Depression and multiple sclerosis

The objective of the present study were (1) to ascertain the lifetime risk of a depression in a representative group of multiple sclerosis (MS) patients, (2) to assess the morbidity risks for depression among first-degree relatives of these MS patients, and (3) to compare these familial risks for first-degree relatives of MS patients with those for first-degree relatives of a primary depression population, i.e., depression but no MS. We psychiatrically evaluated 221 MS patients (index cases) using a structured clinical interview for the DSM-III-R and calculated the rate and lifetime risk of depression for these index cases using the product limit estimate of survival function. We obtained psychiatric histories for all first-degree relatives of index cases, and we calculated morbidity risks for depression for these relatives using the maximum likelihood approach and compared the risks using the likelihood ratio tests. Index cases had a 50.3% lifetime risk of depression. Morbidity risks for depression among first-degree relatives of index cases were decidedly lower when compared with morbidity risks among first-degree relatives of the reference population. Although there appears to be a very high rate of depression among MS patients, the data for their first-degree relatives do not support a clear genetic basis for this depression, or at least the same genetic basis that probably operates within families when depression occurs in the absence of MS.     

Familial aggregation of primary Raynaud's disease

OBJECTIVE: To determine the occurrence of familial aggregation of primary Raynaud's disease. METHODS: Twenty-three patients with primary Raynaud's disease and their first-degree relatives were assessed by questionnaire and, when possible, by physical examination. The same procedures were performed on the patients' spouses and the spouses' first-degree relatives, who served as the control group. RESULTS: The prevalence of Raynaud's disease was significantly higher in the families of the probands than in the control families when assessed by questionnaire (26.1% versus 5.5%; P < 10(-5)), and by physical examination (11.2% versus 2.8%; P = 0.015). CONCLUSION: These findings demonstrate that there is significant familial aggregation of primary Raynaud's disease.     

Etiology of massive obesity: role of genetic factors

It is well established that there is a significant familial aggregation of obesity, although most of the evidence regarding the genetic basis of obesity has been derived from overweight and moderately obese cases. Less is known about the contribution of genetic factors in severely obese individuals. This paper reviews the available evidence regarding the extent of familial aggregation of morbid obesity and the contribution of specific genes. The results of available studies suggest a stronger degree of familial resemblance for morbid obesity [body mass index (BMI > 40 kg/m2)] than for more moderate levels of obesity (BMI < 40 kg/m2). Evidence from human association and linkage studies, performed with markers surrounding human homologs of the genes involved in mouse models of obesity, revealed that these genes tend to be linked more often to severe obesity than to moderate levels of obesity.     

Is the increase in asthma prevalence occurring in children without a family history of atopy?

We investigated the familial associations of asthma and atopic disease in a population in which the prevalence of asthma and atopy is increasing. Interviewer administered abbreviated family history questionnaires were applied in 416 families with a total of 1005 children ascertained through index children attending fracture and dressing clinics. The prevalence of reported asthma (22.5%), eczema (24%) and hayfever (20%) in the children was high but similar to previous studies in this population. Asthma was reported in 20.8% of children of parents without a history of asthma and 18% of children of parents without any history of atopic disease. Logistic regression analysis of outcomes in the index children showed increased risk of atopic disease associated with parental history of the same atopic disease. The presence of an affected sibling was associated with an increased risk of eczema (OR 3.04 CI 1.83-5.05) or hayfever (OR 1.79 CI 0.97-3.3) but not asthma (OR 1.18 CI 0.66-2.08). Increasing number of siblings was associated with reduced risk although this was significant only for hayfever (OR 0.62 CI 0.41-0.86). Although the presence of affected relatives is associated with an increased risk of atopic disease the high prevalence of reported atopic disease, particularly asthma. in children of parents without a family history of atopic disease suggests that much of the increase in asthma prevalence is occurring in children without a significant genetic predisposition. Childhood asthma developing in what would previously have been regarded as low risk families may differ in its aetiology from classical atopic asthma.     

Segregation analysis of plasminogen activator inhibitor-1 and fibrinogen levels in the NHLBI family heart study

Elevated plasminogen activator inhibitor-1 (PAI-1) and fibrinogen concentrations are risk factors for coronary heart disease. We investigated environmental, familial, and genetic influences on PAI-1 antigen and fibrinogen concentrations in 2029 adults from 512 randomly ascertained families in 4 US communities. We used maximum-likelihood segregation analysis to fit several genetic and nongenetic modes of inheritance to the data to determine whether mendelian inheritance of a major gene could best explain the familial distributions of these 2 hemostatic factors. Age- and gender-adjusted familial correlations for PAI-1 antigen level averaged 0.16 in first-degree relatives (95% CI=0.11 to 0.21); the spouse correlation was positive but not statistically significant (r=0.10, 95% CI=-0.02 to 0.23). Complex segregation analysis indicated a major gene associated with higher PAI-1 concentrations in 65% of individuals from these families. Demographic, anthropometric, lifestyle, and metabolic characteristics together explained 37% to 47% of the variation in PAI-1 antigen levels, and the inferred major gene explained an additional 17% of the variance. Positive and statistically significant age- and gender-adjusted familial correlations in first-degree relatives indicated a possible heritable component influencing plasma fibrinogen concentration (r=0. 17, 95% CI=0.13 to 0.22); however, segregation analysis did not provide statistical evidence of a major gene controlling fibrinogen level. These family data suggest that there are modest familial and genetic effects on the concentration of PAI-1.     

Co-morbidity and familial aggregation of alcoholism and anxiety disorders

BACKGROUND: This study examined the patterns of familial aggregation and co-morbidity of alcoholism and anxiety disorders in the relatives of 165 probands selected for alcoholism and/or anxiety disorders compared to those of 61 unaffected controls. METHODS: Probands were either selected from treatment settings or at random from the community. DSM-III-R diagnoses were obtained for all probands and their 1053 first-degree relatives, based on direct interview or family history information. RESULTS: The findings indicate that: (1) alcoholism was associated with anxiety disorders in the relatives, particularly among females; (2) both alcoholism and anxiety disorders were highly familial; (3) the familial aggregation of alcoholism was attributable to alcohol dependence rather than to alcohol abuse, particularly among male relatives; and (4) the the pattern of co-aggregation of alcohol dependence and anxiety disorders in families differed according to the subtype of anxiety disorder; there was evidence of a partly shared diathesis underlying panic and alcoholism, whereas social phobia and alcoholism tended to aggregate independently. CONCLUSIONS: The finding that the onset of social phobia tended to precede that of alcoholism, when taken together with the independence of familial aggregation of social phobia and alcoholism support a self-medication hypothesis as the explanation for the co-occurrence of social phobia and alcoholism. In contrast, the lack of a systematic pattern in the order of onset of panic and alcoholism among subjects with both disorders as well as evidence for shared underlying familial risk factors suggests that co-morbidity between panic disorder and alcoholism is not a consequence of self-medication of panic symptoms. The results of this study emphasize the importance of examining co-morbid disorders and subtypes thereof in identifying sources of heterogeneity in the pathogenesis of alcoholism.     

Poroid hidradenoma. A case presentation

There is no study indicating that informant-derived information on dementia and depression (i.e. family history information) is equivalently valid for first-degree relatives and for index subjects (i.e. patients and control subjects). However, this unproven assumption is the basis for the frequent, possibly inappropriate, use of instruments validated for patients and control subjects in family studies which focus on frequencies of psychiatric disorders in first-degree relatives. Consequently, there is a need to compare the validity of family history information for both disorders in index subjects and their first-degree relatives. Validity was assessed by comparison of family history information for dementia and depression with interview-derived diagnoses in 75 index subjects and 195 age-matched first-degree relatives. The validity of informant-derived information varied for different disorders, i.e. dementia and depression, and different samples, i.e. index subjects and first-degree relatives. In agreement with the study hypothesis, the sensitivity of surrogate information on dementia was significantly reduced in first-degree relatives in comparison with index subjects. In contrast, the sensitivity to detect depression was equivalent in subjects and in relatives. The results indicate the necessity to assess the validity of the psychiatric diagnoses of interest in the sample of interest, e.g. dementia or depression in first-degree relatives of patients and of control subjects. Observations in selected samples, i.e. subjects treated, hospitalised and/or autopsied, cannot be generalised to first-degree relatives in family studies.     

A human lung cancer xenograft producing granulocyte-colony stimulating factor and parathyroid hormone-related protein

BACKGROUND AND PURPOSE: The purpose of the present study was to calculate the prevalence and relative risk of unruptured incidental intracranial aneurysms (IAs) among families with IA case(s) compared with the general population in one geographically defined area in East Finland and to identify the risk group that could benefit most from screening for IAs. We compared these results with our earlier study results of familial IA (FIA) cases, with two or more known IA cases in the same family. METHODS: The study groups were collected from the catchment area of the University Hospital of Kuopio in East Finland. The inclusion criteria were age 30 to 70 years and unruptured incidental IAs > or =3 mm. Patients with previous subarachnoid hemorrhage or in whom a ruptured IA was found to be the cause of death were excluded from all study groups. During routine forensic autopsies the circle of Willis was studied for IAs to estimate the number of IAs in the general population. In the families with one known IA case and in FIA families, MR angiography was used as a preliminary screening method for IAs, followed by intra-arterial angiography to verify suspected IAs. Study populations were age and sex adjusted for the statistical calculations. RESULTS: The relative risk for IAs among first-degree relatives in FIA families was 4.2 (95% confidence interval, 2.2 to 8.0) and among first-degree relatives in families with only one affected family member was 1.8 (95% confidence interval, 0.7 to 4.8) compared with the general population in East Finland. CONCLUSIONS: First-degree relatives in FIA families constitute a high-risk group for incidental IAs, and this group would benefit from screening studies for IAs. Screening for IAs in families with only one affected member or in the general population is not recommended.     

The majority of myeloid-antigen-positive (My+) childhood B-cell precursor acute lymphoblastic leukaemias express TEL-AML1 fusion transcripts

BACKGROUND & AIMS: Crohn's disease and ulcerative colitis show a familial aggregation. In both diseases, anti-goblet cell autoantibodies (GABs) have been described. The aim of this study was to define the role of GABs in the pathogenesis of inflammatory bowel disease. METHODS: The study population comprised 61 patients with ulcerative colitis, 76 patients with Crohn's disease, 101 first-degree relatives of patients with ulcerative colitis, and 105 first-degree relatives of patients with Crohn's disease. Thirty-five patients with infectious enterocolitis and 56 healthy unrelated subjects served as controls. Autoantibodies were detected by indirect immunofluorescence. RESULTS: Thirty-nine percent of patients with ulcerative colitis (24 of 61) and 30% of patients with Crohn's disease (23 of 76) were positive for GABs. GABs were detected in 21% (21 of 101) of first-degree relatives of patients with ulcerative colitis and in 19% (20 of 105) of first-degree relatives of patients with Crohn's disease. In patients with infectious enterocolitis and in healthy controls, GABs were seen in 3% (1 of 35) and 2% (1 of 56), respectively. The differences between control groups and both groups of patients or their first-degree relatives were significant. CONCLUSIONS: The high prevalence in first-degree relatives suggests that GABs may represent a marker characterizing susceptibility to inflammatory bowel disease.     

HLA-DQB1-defined genetic susceptibility, beta cell autoimmunity, and metabolic characteristics in familial and nonfamilial insulin-dependent diabetes mellitus. Childhood Diabetes in Finland (DiMe) Study Group

Familial aggregation of insulin-dependent diabetes mellitus (IDDM) is a common phenomenon, but the reasons behind it are poorly understood. To investigate whether there is heterogeneity between familial and nonfamilial forms of IDDM we compared genetic, immunological, and clinical characteristics of diabetic children with and without an affected first-degree relative in a population-based series of Finnish children with IDDM. The frequencies of HLA-DQB1 genotypes known to be associated with high (DQB1*0302/0201) or moderate (*0302/x) IDDM risk in the Finnish population were increased, while the proportions of DQB1 genotypes associated with low or decreased risk for IDDM were reduced in the 121 familial cases as compared with the 574 nonfamilial cases (32.7 vs. 21.3%, 41.3 vs. 35.9%, 18.3 vs. 31.4%, and 7.7 vs. 11.4%, respectively; P = 0.002). The frequencies and serum concentrations of islet cell antibodies, insulin autoantibodies, and antibodies to the 65-kD isoform of glutamic acid decarboxylase were similar at diagnosis in the familial and nonfamilial cases. The 31 first-affected cases in the multiple case families were younger at diagnosis than the nonfamilial cases (6.9 vs. 8.5 yr; P < 0.05). The 90 second-affected familial cases had less severe metabolic decompensation at diagnosis than either the first-affected familial or nonfamilial cases. In conclusion, familial aggregation of IDDM in Finland is at least partly explained by a higher frequency of IDDM susceptibility genes in families with multiple affected individuals. The lack of differences in autoantibody levels between the familial and nonfamilial cases indicates homogeneity rather than heterogeneity in the pathogenetic process of beta cell destruction.     

Familial clustering of end-stage renal disease in blacks with lupus nephritis

The factors that determine a patient's susceptibility to specific target organ involvement in systemic lupus erythematosus (SLE) remain unknown. Lupus nephritis can be a particularly devastating complication, with an increased mortality and the risk of progressive renal damage resulting in end-stage renal disease (ESRD). This analysis was performed to determine whether renal disease aggregated in select families or was a sporadic complication in patients with SLE. We compared the family history of ESRD in 50 patients with SLE complicated by lupus nephritis with 37 controls who had SLE but lacked nephritis after a mean follow-up duration of more than 11 years. The frequency of relatives with ESRD in the lupus nephritis cases was compared with that in controls using Fisher's exact test (significance at P < or = 0.05). Fifty percent (25) of the 50 lupus nephritis patients were black and 50% (25) white, in contrast to 35% (13) and 65% (24) of the 37 lupus non-nephropathy controls, respectively. A first-, second-, or third-degree relative with ESRD was present in 16% (eight) of the 50 lupus nephritis cases and in 0% of the 37 SLE non-nephropathy controls (P = 0.019, Fisher's exact test, two-tail). Twenty-eight percent (seven) of the 25 black patients with lupus nephritis had relatives with ESRD compared with 0% of the 13 black lupus non-nephritis controls (P = 0.07). Only one of the eight relatives with ESRD had SLE or a collagen vascular disease. Lupus nephritis patients and the non-nephritis controls had similar ages (mean +/- SD: 38.5 +/- 10.0 years v 46.6 +/- 11.8 years; P = 0.28), family sizes (6.27 +/- 2.61 first-degree relatives v 6.35 +/- 3.25 first-degree relatives; P = 0.16), and duration of SLE (9.26 +/- 5.94 years v 11.35 +/- 6.43 years; P = 0.60). Familial clustering of ESRD was observed in black patients with SLE who had nephritis. This was unlikely to be related to differences in patient age, family size, or duration of SLE. This data, coupled with the known familial aggregation of ESRD in blacks with hypertensive and diabetic ESRD, supports the contention that genetic factors contribute to the familial clustering. The presence of relatives with etiologies of ESRD other than SLE suggests that there is an inherited susceptibility to progressive renal failure, independent of the etiology of ESRD.     

Li-Fraumeni syndrome in pediatric patients with soft tissue sarcoma or osteosarcoma

Family history of cancer and features of the Li-Fraumeni syndrome (LFS) were investigated in 42 patients with soft tissue sarcoma or osteosarcoma in a pediatric hospital in Mexico City, and compared with 42 non-cancer children. Six subjects with cancer were found among 204 first-degree relatives of cancer patients while there were none among 183 first-degree relatives of non-cancer children. In three families, the proband had two affected relatives, and the type of neoplasia as well as the age of onset suggested the clinical diagnosis of LFS. Our results show that 7.1% of our pediatric patients with soft tissue sarcoma or osteosarcoma may belong to LFS families. The authors encourage pediatric and adult oncologists to pay more attention to the history of cancer in nuclear families for eventual hereditary cancer syndrome identification and cancer prevention.     

Genetic polymorphisms in catechol-O-methyltransferase, menopausal status, and breast cancer risk

Polymorphic catechol-O-methyltransferase (COMT) catalyzes the O-methylation of estrogen catechols. In a case-control study, we evaluated the association of the low-activity allele (COMT(Met)) with breast cancer risk. Compared to women with COMT(Val/Val), COMT(Met/Met) was associated with an increased risk among premenopausal women [odds ratio (OR), 2.1; confidence interval (CI), 1.4-4.3] but was inversely associated with postmenopausal risk (OR, 0.4; CI, 0.2-0.7). The association of risk with at least one low-activity COMT(Met) allele was strongest among the heaviest premenopausal women (OR, 5.7; CI, 1.1-30.1) and among the leanest postmenopausal women (OR, 0.3; CI, 0.1-0.7), suggesting that COMT, mediated by body mass index, may be playing differential roles in human breast carcinogenesis, dependent upon menopausal status.     

Aggressive therapy in patients with heart failure]

The potential role of genetic factors in the etiology of posttraumatic and alcohol-associated seizures was studied in 289 male patients with recurrent seizures and in 174 individuals who had never experienced a seizure. The incidence of seizures in first-degree relatives of probands was compared with that in relatives of unaffected individuals. Relatives of patients with alcohol-associated seizures had a rate ratio of 2.45 [95% confidence interval (CI) 1.41-4.25], whereas no excess incidence was noted among relatives of posttraumatic epilepsy patients (rate ratio 1.20, 0.64-2.25 CI). Relatives of probands with both antecedents showed an intermediate rate ratio of 1.72 (0.92-3.20 CI). Among probands with alcohol-associated seizures, the rate ratio of 2.05 for patients with alcohol-related seizures (i.e., spontaneously occurring seizures in association with chronic alcohol abuse) was slightly higher than that of 1.85 for probands with alcohol withdrawal seizures. Trauma severity had a slight impact on the incidence of affected relatives; patients with severe head injuries had a rate ratio of 0.73 and probands with milder trauma had a rate ratio of 0.99. The results indicate a limited, if any, role of genetic predisposition in development of posttraumatic seizures. Alcohol-related seizures, however, showed familial aggregation of unprovoked seizures, suggesting an involvement of genetic factors in the origin of such seizures.     

Patterns of inheritance of ovarian cancer. An analysis from an ovarian cancer screening program

BACKGROUND: A variety of inheritance patterns for familial ovarian cancer have been proposed including an autosomal dominant inheritance, a breast-ovary cancer syndrome and Lynch Cancer Family Syndrome (involving breast, bowel, ovary, and endometrial cancers). METHODS: Women participating in an ovarian cancer screening study completed a questionnaire concerning their family history of ovarian and other malignancies (in particular breast, bowel, and endometrial cancer). Confirmation of the diagnosis was sought when there was uncertainty. RESULTS: Two hundred forty women with a first-degree relative with ovarian cancer participated in the study. Nine percent of these women (representing 13 families) gave a definite history of two or more affected first-degree relatives. Two families had a pedigree consistent with an autosomal dominant inheritance. A breast-ovary cancer family and a Lynch cancer family syndrome were suspected in one family each, although 34% of all women gave a history of at least one other first-degree relative with either breast, bowel, or endometrial cancer. CONCLUSIONS: Only a small number of women with a family history of ovarian cancer fit into the recognized hereditary patterns. Difficulty in recognizing the inheritance patterns and the lack of definitive genetic markers poses problems in providing adequate counseling regarding screening and prophylactic oophorectomy.     

Interferon-gamma-activated monocytes impair infectivity of HIV particles by an oxygen metabolite-dependent reaction

Heterozygous familial hypercholesterolemia (FH) is a serious disorder causing twice normal low-density lipoprotein cholesterol levels early in childhood and very early coronary disease in both men and women. Treatment with multiple medications and diet can normalize cholesterol levels in many persons with FH and prevent or delay the development of coronary atherosclerosis. Thus, there is a need for accurate and genetically validated criteria for the early diagnosis of heterozygous FH. Previously published blood cholesterol criteria greatly underdiagnosed new cases of FH among members of known families with FH in Utah and overdiagnosed FH among participants of general population screening, revealing the need for different cholesterol screening criteria in persons from these 2 different settings. The statistical concept of a priori probabilities was applied to derive 2 sets of practical screening criteria: one for persons participating in general population screening studies and another for close relatives of confirmed FH cases, showing dramatic differences. At a cholesterol level of 310 mg/dl, only 4% of persons in the general population would have FH but 95% of persons who were first-degree relatives of known cases would have FH. Detailed tables were derived to provide practical total and low-density lipoprotein blood cholesterol screening criteria for diagnosing FH in different screening settings and specific age groups. In population screening the new FH criteria require a total cholesterol > 360 mg/dl for age 40+ (or 270 mg/dl in youth). Among first-degree relatives of confirmed cases in families with FH, the new total cholesterol criteria are much lower (> 290 mg/dl for age 40+, > 220 mg/dl for youth).(ABSTRACT TRUNCATED AT 250 WORDS)     

Risk factors for lung cancer in young adults

Risk factors for early onset of lung cancer are relatively unknown. In a case-control study, carried out in Germany between 1990 and 1996, the effects of smoking and familial aggregation of cancer were compared in 251 young cases and 280 young controls (< or = 45 years) and in 2,009 older cases and 2,039 older controls (55-69 years). The male/female ratio was 2.6/1 in young patients and 5.6/1 in older patients. Adenocarcinomas were more frequent in young men than in older men (41 % vs. 28%). Duration of smoking and amount smoked showed significantly increased odds ratios for lung cancer in both age groups. Lung cancer in a first degree relative was associated with a 2.6-fold (95% confidence interval (CI) 1.1-6.0) increase in the risk of lung cancer in the young age group, but no elevated risk was seen in the older group (OR = 1.2, 95% CI 0.9-1.6). Smoking-related cancer in relatives with the age at diagnosis under 46 years was associated with an increased risk of lung cancer in the young group (OR = 5.6, 95% CI 0.7-46.9) but not in the older group (OR = 0.7, 95% CI 0.3-1.5). Results indicated that lung cancer risk in young and older age groups shows remarkable differences with respect to sex, histologic type, and genetic predisposition.     

Effect of BRCA1 and BRCA2 on the association between breast cancer risk and family history

BACKGROUND: The discovery of BRCA1 and BRCA2 has led to a reassessment of the association between family history of breast/ovarian cancer and breast cancer risk after controlling for carrier status for mutations in the BRCA1 and BRCA2 genes. We examined whether family history of breast cancer remains a predictive risk factor for this disease after carrier status for BRCA1 and/or BRCA2 mutations is taken into consideration. METHODS: The data are from 4730 case subjects with breast cancer and 4688 control subjects enrolled in the Cancer and Steroid Hormone Study. The probability of being a BRCA1 and/or BRCA2 gene carrier was calculated for each woman. Among predicted noncarriers, logistic regression was used to assess the relationship (odds ratios and 95% confidence intervals [CIs]) between case or control status and family history of breast or ovarian cancer. Estimates of age-specific breast cancer risk are presented by predicted carrier status. RESULTS: Among predicted noncarriers, case subjects were 2.06 times (95% CI = 1.69-2.50) and 1.24 times (95% CI = 1.17-1.32) more likely to report a first-degree or second-degree family history of breast cancer, respectively, than were control subjects. Case subjects were 1.99 times (95% CI = 1.63-2.44), 1.66 times (95% CI = 1.18-2.38), and 2.23 times (95% CI = 0.21-24.65) more likely to report an affected mother, sister, or both, respectively, than were control subjects. A family history of ovarian cancer was not statistically significantly associated with breast cancer risk. Noncarriers were predicted to have a lifetime risk of 9% of developing breast cancer compared with a 63% risk for carriers. CONCLUSIONS: Among women with a moderate family history of breast cancer, i.e., predicted noncarriers of BRCA1 and/or BRCA2 mutations, family history remains a factor in predicting breast cancer risk. In families with breast and ovarian cancers, the aggregation of these two cancers appears to be explained by BRCA1/BRCA2 mutation-carrier probability.     

Blood transfusion, smoking, and obesity as risk factors for the development of rheumatoid arthritis: results from a primary care-based incident case-control study in Norfolk, England

OBJECTIVE: To examine a range of demographic, social, and clinical risk factors for the development of rheumatoid arthritis (RA). METHODS: Population-based case-control study in Norfolk, England, involving adult patients, ages 18-70, with an inflammatory polyarthritis of <12 months' duration who were recruited from the Norfolk Arthritis Register. Controls, matched for sex and date of birth, were selected from the primary care register of the Norwich Health Authority. Both cases and controls completed identical self-administered questionnaires. Matched analysis of the 165 case-control sets was conducted for the whole group and for the subset in which the cases satisfied the 1987 American College of Rheumatology criteria for RA. RESULTS: The controls were of higher socioeconomic status than the cases. This was probably due to response bias. Having a body mass index > or =30 was associated with an adjusted odds ratio (OR) of 3.74 for developing RA (95% confidence interval [95% CI] 1.14-12.27). RA was also associated with a history of blood transfusion (OR 4.83, 95% CI 1.29-18.07). Even after correcting for social class, a history of having ever smoked was associated with a higher risk of developing RA (OR 1.66, 95% CI 0.95-3.06). There was no difference between cases and controls in previous exposure to childhood infections, certain surgical procedures, or reproductive history variables. CONCLUSION: RA has a number of potential environmental triggers, including smoking, obesity, and blood transfusion.     

Genetic susceptibility and head injury as risk factors for Alzheimer's disease among community-dwelling elderly persons and their first-degree relatives

We performed a community-based study to investigate the relationship of genetic susceptibility and head injury to Alzheimer's disease (AD) in 138 patients with AD and 193 healthy elderly control subjects. Data concerning presence or absence of dementia and certain exposures were also obtained from 799 first-degree relatives of the patients and 1,238 first-degree relatives of the control subjects. Adjusting for age, gender, and other risk factors, the odds ratio for AD associated with head injury was 3.7 (95% confidence interval [CI], 1.4-9.7). The association was highest for head injuries that occurred after age 70. The risk of AD was higher in first-degree relatives of patients with onset prior to age 70 than in relatives of control subjects (risk ratio [RR] = 2.5; 95% CI, 1.1-5.6). The risk was not increased for relatives of patients with onset of AD at age 70 or older. Compared with relatives without head injury, the risk of AD was increased among both head-injured relatives of patients (RR = 5.9; 95% CI, 2.3-14.8) and head-injured relatives of control subjects (RR = 6.9; 95% CI, 2.5-18.9). Our results are consistent with the hypothesis that severe head injury and genetic susceptibility are associated with AD. Both associations concur with current concepts regarding the role of amyloid in AD. Although we regard head injury, like genetic susceptibility, to be a putative risk factor for AD, the temporal relationship between head injury and AD warrants further investigation.