HLA-DRB1*0701 and DRB1*1401 are associated with genetic susceptibility to psoriasis vulgaris in a Taiwanese population

We analysed the allelic frequencies of class II human leucocyte antigen (HLA)-DRB1, DQA1, DQB1 and DPB1 by polymerase chain reaction/sequence-specific oligonucleotide probe hybridization typing in 76 Taiwanese psoriasis vulgaris (PSV) patients and 238 Taiwanese non-psoriatic controls. The analysis revealed the following: (i) the DRB1*0701 allele was positively associated with PSV (relative risk, RR = 6.4, corrected P-value, Pc < or = 0.001); (ii) the DRB1*1401 allele was positively associated with type I PSV (age at onset < 40 years) (RR = 3.5, Pc < or = 0.001); (iii) the DQA1*0501 allele was negatively associated with PSV (RR = 0.4, Pc < or = 0.001); (iv) there was no significant association of HLA-DP genes with PSV; and (v) there was a strong association of beta-chain phenylalanine at position 37 (Phe 37) and glutamate or glutamine at position 74 (Glu 74/Gln 74) with PSV (RR = 3.5, Pc < or = 0.001 for the association of Phe 37 with PSV: RR = 2.2, Pc < or = 0.001 for the association of Glu 74/Gln 74 with PSV). The positive association between PSV and the DRB1*0701 allele is consistent with previous reports. The negative association of the DQA1*0501 allele is reported only in Finland, whereas the positive association between PSV and the DRB1*1401 allele has never been described before. Trans-racial studies may shed further light on the association of class II HLA alleles or other closely linked genes with the development of PSV. Phe 37 (a large, non-polar amino acid) and Glu 74/Gln 74 (both negatively charged amino acids) were the polymorphic residues in pockets 9 and 4, respectively, of the beta-chain, which may have increased their affinity for the small non-polar amino acids and basic amino acids of the psoriatic antigen peptide, thereby activating the T lymphocytes. This finding may facilitate the identification of a psoriatic antigen.     

Analysis of HLA-DRB1-related alleles in Japanese patients with lung cancer--relationship to genetic susceptibility and resistance to lung cancer

PURPOSE: To investigate differences in HLA status among lung cancer patients, patients with hematological malignancies, and healthy controls in order to determine the genetic susceptibility and resistance features of HLA-DRB1-related alleles in Japanese patients with lung cancer. METHODS: HLA class I (HLA-A, -B, and -C) antigens and HLA class II (HLA-DRB1) alleles were determined in 36 patients with lung cancer, 35 patients with hematological malignancies, and 90 healthy controls. HLA class I status was investigated by serological techniques, and HLA class II by polymerase chain reaction/restriction-fragment-length polymorphism analysis. RESULTS: Lung cancer patients showed an increased frequency of HLA-DRB1*0901, and a decreased frequency of HLA-DRB1*1302 and DRB1*14-related alleles when compared to the other subjects. CONCLUSION: These results suggest that genetic factors influence the susceptibility and resistance to lung cancer. However, this study should be considered preliminary because of the relatively small number of patients examined and the possibility of racial differences in HLA status of lung cancer patients between Japan and other countries.     

DRB1*15 and DRB1*03 extended haplotype interaction in primary Sj?gren's syndrome genetic susceptibility

OBJECTIVE: Sj?gren's syndrome (SS) is a chronic autoimmune disease with a genetic component. Among the genetic factors, the role of HLA class II genes has been suggested and a positive association with DRB1*03 allele has been described. However, there is no consensus on a unique HLA locus for this disease nor on the role of the HLA gene product in the disease. The aim of this study was to analyse prospectively MHC region involvement in the genetic susceptibility to SS by studying DRB1, DQB1, DPB1, TAP1, TAP2 genes and TNF microsatellites in a population of 45 primary SS patients. METHODS: All the polymorphisms studied were analysed at the genomic level using PCR-based methodologies. RESULTS: Concerning HLA class II alleles, the highest relative risk to develop the disease was associated with the DRB1*15-DRB1*0301 heterozygous genotype (17.8% vs 3.5% in controls - pc < 0.005, OR = 5.96). Analysing other genes located on the same region allowed us to further determine the DRB1 haplotypes at risk. For instance, the DRB1*0301 haplotype involved in the genetic susceptibility to SS was more often associated with the DPB1* 0201 and TNF-a2 alleles in SS patients than in controls. Moreover, all the DRB1*15-DRB1*0301 SS patients were TAP1-0101, TAP2-0101 homozygous, allowing us to deduce the extended genotype at risk as DRB1*15, TAP1-0101, TAP2-0101/DRB1*0301, TAP1-0101, TAP2-0101 which was carried by only 3 controls out of the 130 tested (p < 0.01, OR = 6.68). CONCLUSION: This study confirmed the role of the MHC region in the susceptibility to Sj?gren's disease, and for the first time suggests a synergistic interaction between two HLA-DRB1 extended haplotypes in the genetic mechanisms controlling the disease.     

Frequency of loci of HLA-DRB1* and -DQB1* alleles in the Slovak population]

Results on HLA-DRB1* and HLA-DQB1* allele frequencies in the Slovak population by PCR-SSP method are presented. HLA-DRB1* alleles were determined in 130 and HLA-DQB1* alleles in 143 healthy unrelated individuals. The highest frequency was observed for the alleles HLA-DRB1*1101-13 (0.203), HLA-DRB1*0701 (0.142), HLA-DQB1*0301 (0.244), and HLA-DQB1*0201 (0.209). The least frequent alleles were HLA-DRB1*1402-6-9, HLA-DRB1*0901 (both 0.0038), HLA-DQB1*0401 (0.007), and HLA-DQB1*0601 (0.0035). The results obtained by DNA-typing were compared with those calculated from the serological study. No statistically significant differencies were found. The allele frequencies obtained in our study were also compared with those of the Czech and Austrian populations. No statistically significant differencies were observed. (Fig. 2, Tab. 3, Ref. 13.)     

HLA-DRB and -DQB1 alleles in Polish patients with hepatitis B associated membranous nephropathy

The lower blepharoplasty procedure has had numerous surgical variations described and remains a challenge to those performing the operation. Disappointments with the technique revolve around complications such as lateral third scleral show, hollow sunken eyelids, rounding of the eye and overall long-term, tired, drawn appearance of the lower lids. Multiple adjuncts to the blepharoplasty procedure have been described. These vary in their difficulty of execution and associated complications. The concept of internal muscle suspension has been accepted as a successful adjunct by many authors but often the technique chosen has been a complicated one, adding time and complexity to the procedure.     

HLA-DRB1 alleles and beta 2 glycoprotein I-dependent anticardiolipin antibodies in Japanese patients with systemic lupus erythematosus

PURPOSE: This study was designed to evaluate the anatomic and functional consequences of lateral internal sphincterotomy in patients who developed anal incontinence and in matched controls. METHODS: The study includes 13 patients with anal incontinence after lateral internal sphincterotomy and 13 controls who underwent the same operation and were continent and satisfied with the results of the procedure. Patients underwent clinical evaluation, anorectal manometry, pudendal nerve terminal motor latency testing, and endoanal ultrasonography. RESULTS: Sphincterotomies were longer in incontinent patients (75 vs. 57 percent), but the resting pressure and length of the high-pressure zone were not different between groups. Surprisingly, maximum voluntary contraction was higher in incontinent patients than in continent controls (136 vs. 100 mmHg). Rectal sensation and pudendal nerve terminal motor latency were similar in both groups. The defect in the internal sphincter was wider in incontinent patients than in continent controls (17.3 vs. 14.4 mm), but these differences were not statistically significant. The thickness of the internal sphincter measured by endoanal ultrasound was identical in both groups, but the external sphincter was thinner in incontinent patients both at the site of the sphincterotomy (6.8 vs. 8.1 mm) and in the posterior midline (7.1 vs. 8.6 mm). CONCLUSIONS: Anal incontinence after lateral internal sphincterotomy is directly related to the length of the sphincterotomy. Whether secondary to preoperative sphincter abnormality or the result of lateral internal sphincterotomy, the external sphincter is thinner in incontinent patients than in continent controls.     

Use of T cell receptor/HLA-DRB1*04 molecular modeling to predict site-specific interactions for the DR shared epitope associated with rheumatoid arthritis

OBJECTIVE: To use molecular modeling tools to analyze the potential structural basis for the genetic association of rheumatoid arthritis (RA) with the major histocompatibility complex (MHC) "shared epitope," a set of conserved amino acid residues in the third hypervariable region of the DRbeta chain. METHODS: Homology model building techniques were used to construct molecular models of the arthritis-associated DRB1*0404 molecule and a T cell receptor (TCR) from T cell clone EM025, which is specific for DR4 molecules containing the shared epitope sequence. Interactive graphics techniques were used to orient the TCR on the DR molecule, guided by surface complementarity analysis. RESULTS: The predicted TCR-MHC-peptide complex involved multiple interactions and specificity for the shared epitope. TCR residues CDR1beta D30, CDR2beta N51, and CDR3beta Q97 were positioned to potentially participate in hydrogen bond interactions with the shared epitope DRbeta residues Q70 and R71. CONCLUSION: These results suggest a structural mechanism in which specific TCR recognition and possibly Vbeta selection are directly influenced by the disease-associated MHC polymorphisms.     

Relative predispositional effects and mode of inheritance of HLA-DRB1 alleles among community-based Caucasian females with rheumatoid arthritis

This review addresses two questions. First, why does clozapine apparently occupy low levels of dopamine D2 receptors in patients, in contrast to all other antipsychotic drugs which occupy 70-80% of brain dopamine D2 receptors? Second, what is the receptor basis of action of antipsychotic drugs which elicit low levels of Parkinsonism? Antipsychotic doses of clozapine occupy between 0% and 50% of D2 receptors, as measured in patients by a variety of radioligands. It has recently been found, however, that the percent occupancy of a receptor by a drug depends on the radioligand used to measure that receptor. Based on this new finding, this review concludes that clozapine clinically occupies high levels of D2 receptors in the absence of any radioligand. This occupancy is estimated to be of the order of 70-80% in the dopamine-rich region of the human striatum, and even higher in the limbic D2-containing regions which are low in endogenous synaptic dopamine. This conclusion arises from two different approaches. One approach is to relate the reported clozapine occupancies in the human striatum with the dissociation constants of the various radioligands at the D2 receptor. This relation extrapolates to approximately 70-80% occupancy by clozapine when clozapine competes with endogenous dopamine at the D2 receptor. The second approach is to calculate the D2 occupancy of each antipsychotic drug, using the average spinal fluid concentration and the correct dissociation constant of the antipsychotic, thereby revealing that all antipsychotic drugs, including clozapine, occupy approximately 70-80% of dopamine D2 receptors in the human striatum, and possibly higher in the limbic regions. As determined by the new dissociation constants, antipsychotic drugs which elicit Parkinsonism (trifluperazine, chlorpromazine, raclopride, haloperidol, fluphenazine, risperidone) bind more tightly than dopamine to D2, while those antipsychotic drugs which elicit little or no Parkinsonism (melperone, seroquel, perlapine, clozapine, remoxipride, molindone, sulpiride, olanzapine, sertindole) bind more loosely than dopamine to D2 receptors. Compared to the tightly bound antipsychotic drugs, the more loosely bound antipsychotics generally require higher clinical doses, require fewer days for clinical adjustment, but may dissociate from the D2 receptor more rapidly and could lead to clinical relapse somewhat earlier than that found with the traditional tightly bound antipsychotic drugs.     

Contribution of DRB1*04 variants to predisposition to or protection from insulin dependent diabetes mellitus is independent of dq

Certain DQ alpha/beta dimeric molecules have been shown to play a major role in determining susceptibility or resistance to IDDM. Whether or not predisposition associated with DR4 haplotypes is exclusively due to linkage to DQB1*0302 and DQA1*0301 alleles is still a controversial issue. A modifying effect of certain DRB1*04 subtypes on the susceptibility encoded by DQ alleles is possible, since not all DRB1*04-DQB1*0302 haplotypes are associated with the disease. The distribution of DRB1*04 subtypes was analysed in 240 DR4-positive Caucasian IDDM patients and 110 DR4-positive healthy controls using allele-specific hybridization after genomic amplification. Although an important contribution to IDDM predisposition was encoded by the DQB1*0302 allele which was found in the majority of patients (94.2% vs 64.7% in controls, Odd's ratio OR = 8.8, P < 0.0001), differences between DRB1*04 variants persisted after the effect of the DQB1 locus was removed by matching patients and controls for DQB1*0302. Thus, the DRB1*0402 allele conferred a strong IDDM-predisposing effect (OR = 3.1, P < 0.02) which was highly significant in the absence of DR3 on the second haplotype (OR = 5.6, P < 0.0001) but was not visible among DR3/4 heterozygote individuals. Conversely, the DRB1*0404 allele conferred a strong protective effect (OR = 0.26, P < 0.0001) which was dominant even in the presence of the associated high risk DR3 haplotype (OR = 0.21, P < 0.03). These data indicate that DQ molecules are not the sole contributors to the DR4-associated IDDM predisposition, and that peculiar DR4 subtypes play a significant role in susceptibility to or protection from the disease. DRB1*0402 differs from DRB1*0404 by only two acidic residues at positions 70 and 71 within the peptide binding groove, instead of amide and basic amino acids. This might induce changes of peptide binding specificity that correlate with the genetic linkage of IDDM predisposition.     

A transmission/disequilibrium study of the DRB1*04 gene locus on chromosome 6p21.3 with schizophrenia

The precise relationship of the components of the heart can be difficult to understand. With recent developments in cardiac ultrasound and other imaging modalities, most professionals need to be familiar with cross-sectional cardiac anatomy. We have created a teaching technique based on a normal human heart removed at autopsy. It was scanned using a computed tomography scanner and the images examined in different planes. The images were annotated and used in a computer-based teaching program to convey the details of cardiac anatomy. Images corresponding to planes typically used in echocardiography were also examined. The resulting images were of high resolution and illustrated many subtle structures rarely seen in conventional studies of cardiac anatomy. This system has benefits to both clinicians and anatomists.     

HLA class I and II alleles and susceptibility to generalized pustular psoriasis: significant associations with HLA-Cw1 and HLA-DQB1*0303

HLA alleles in generalized pustular psoriasis (GPP) were investigated to clarify the etiology and/or pathogenesis of this disease. Not only serological typing of HLA class I and II antigens but also genotyping of HLA class II alleles were carried out in twenty-six unrelated Japanese patients with GPP. These patients were classified according to their history of psoriasis vulgaris (PV). Serological typing revealed a significantly high incidence of HLA-Cw1 (Pc = 0.04) in the patients as compared with Japanese healthy controls. The frequency of HLA-B46 was particularly high in the patients with GPP and a previous history of PV. Genotyping of HLA class II alleles showed a highly significant increase in HLA-DQB1*0303 (Pc = 0.01) in the patients vs. the healthy controls. In particular, HLA-DQB1*0303 was significantly more frequent in the patients with no prior history of PV than in those with a history of PV. Analysis on linkage disequilibrium showed remarkably different patterns for HLA class II haplotypes between the patients and the healthy controls. Based on the comparative analysis among the amino acid sequences of the beta 1-domain of the HLA-DQB1*03 alleles, proline at residue 55 was suggested to be important as a common amino acid for determination of the susceptibility to GPP. These results revealed not only an association between the etiology and/or pathogenesis of GPP and HLA, but also different mechanisms of the immune response between the patients with GPP and PV.     

Combined effect of HLA-DRB1*1501 and interleukin-1 receptor antagonist gene allele 2 in susceptibility to relapsing/remitting multiple sclerosis

Susceptibility to multiple sclerosis (MS) is associated with HLA-DRB1*1501. Many reports have suggested associations with other loci but these results remain unconfirmed. We studied the IL-1 receptor antagonist (IL-1ra) gene polymorphism and the HLA-DR and DQ allele frequencies by DNA-based methods in both the primary chronic progressive form (PP MS) and the relapsing/remitting form (R/R MS). The frequency of DRB1*1501 and IL-1ra allele 2 were significantly higher in R/R MS. Association was more marked in the female sex and in patients with benign forms of R/R MS. On the other hand DR4 subtypes carrying a Val at position 86 in the DR beta chain were increased in PP MS. The present study indicates that MS is genetically heterogeneous and shows a combined effect of HLA-DR and IL-1ra genes in susceptibility to the R/R form of the disease.     

Major histocompatibility complex class II DR alleles DRB1*1501 and those encoding HLA-DR13 are preferentially associated with a diminution in maternally transmitted human immunodeficiency virus 1 infection in different ethnic groups: determination by an automated sequence-based typing method

Transmission of human immunodeficiency virus 1 (HIV-1) from an infected women to her offspring during gestation and delivery was found to be influenced by the infant's major histocompatibility complex class II DRB1 alleles. Forty-six HIV-infected infants and 63 seroreverting infants, born with passively acquired anti-HIV antibodies but not becoming detectably infected, were typed by an automated nucleotide-sequence-based technique that uses low-resolution PCR to select either the simpler Taq or the more demanding T7 sequencing chemistry. One or more DR13 alleles, including DRB1*1301, 1302, and 1303, were found in 31.7% of seroreverting infants and 15.2% of those becoming HIV-infected [OR (odds ratio) = 2.6 (95% confidence interval 1.0-6.8); P = 0.048]. This association was influenced by ethnicity, being seen more strongly among the 80 Black and Hispanic children [OR = 4.3 (1.2-16.4); P = 0.023], with the most pronounced effect among Black infants where 7 of 24 seroreverters inherited these alleles with none among 12 HIV-infected infants (Haldane OR = 12.3; P = 0.037). The previously recognized association of DR13 alleles with some situations of long-term nonprogression of HIV suggests that similar mechanisms may regulate both the occurrence of infection and disease progression after infection. Upon examining for residual associations, only only the DR2 allele DRB1*1501 was associated with seroreversion in Caucasoid infants (OR = 24; P = 0.004). Among Caucasoids the DRB1*03011 allele was positively associated with the occurrence of HIV infection (P = 0.03).     

Mutant PCNA alleles are associated with cdc phenotypes and sensitivity to DNA damage in fission yeast

Twenty-eight site-directed mutations were introduced into the fission yeast gene (pcn1+) that encodes proliferating cell nuclear antigen (PCNA) and their in vivo effects analyzed in a strain with a null pcn1 background. Mutants defective in enhancing processivity of DNA polymerase delta have previously been identified. In this study, we assessed all of the mutants for their sensitivities to temperature, hydroxyurea, UV irradiation and methyl methanesulfonate (MMS), and specific mutants were also tested for sensitivity to gamma irradiation. One cold-sensitive allele, pcn1-3, was characterized in detail. This mutant had a recessive cold-sensitive cdc phenotype and showed sensitivity to hydroxyurea, UV, and gamma irradiation. At the non-permissive temperature pcn1-3 protein was able to form homotrimers in solution and showed increased stimulation of both synthetic activity and processivity of DNA polymerase delta relative to the wild-type Pcn1+ protein. Epistasis analyses indicated that pcn1-3 is defective in the repair pathway involving rad2+ but not defective in the classical nucleotide excision repair pathway involving rad13+. Furthermore, pcn1-3 is either synthetically or conditionally lethal in null checkpoint rad backgrounds and displays a mitotic catastrophe phenotype in these backgrounds. A model for how pcn1-3 defects may affect DNA repair and replication is presented.     

HLA-DRB1 and tumor necrosis factor gene polymorphisms in Japanese patients with multiple sclerosis

A significant difference between cytosolic and chloroplastic fructose-1,6-bisphosphatase (FbPase) is an extra peptide in the middle of chloroplast FbPase which contains three additional cysteine residues. Sit-directed mutagenesis experiments have shown that at least two of these cysteine residues are involved in forming the regulatory disulfide bridge [Jacquot, J.-P. et al., FEBS Lett. 401 (1997) 143-147] which is the presupposition for the thioredoxin-dependent control of chloroplast FbPase activity. Here we report that each subunit of the FbPase contains an additional structural disulfide bridge which has been observed by combined application of thioredoxins and sulfitolysis. Observation of the structural disulfide bridges by sulfitolysis was only possible when the FbPase was already specifically reduced by the homologous thioredoxin species TRm. and TRf from spinach chloroplasts. Interestingly, the accessibility of the structural disulfide bridge for sulfite ions depends on the thioredoxin species engaged in the thioredoxin/FbPase complex.     

Association to HLA-DRB1*08, HLA-DPB1*0301 and homozygosity for an HLA-linked proteasome gene in juvenile ankylosing spondylitis

To assess the role of HLA genes other than those encoding B27 in predisposing to JAS and AAS, we analyzed the distribution of B*4001, as well as the DRB1, DPB1, and LMP2 alleles, using PCR-based techniques in 63 JAS and 44 AAS patients (all B27 positive). The NBMDR (N = 4724) provided a source of controls matched with the patients for B27 (or other markers when necessary). We found an increase of the B*4001, DRB1*08, and DPB1*0301 alleles, as well as the LMP2 b/b genotype (the latter was most pronounced among patients with acute iridocyclitis), in JAS compared to B27-positive controls. The increase of DRB1*08 and DPB1*0301 was due to an increase of DRB1*08 and DPB1*0301 in combination, whereas the association with B*4001 could be due to linkage disequilibrium with LMP2b. None of these associations were detected in AAS. We conclude that in JAS, in addition to the association to B27, there are also weaker but distinct associations to the DRB1*08, DPB1*0301 alleles and homozygosity for LMP2b.     

Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population

An association of lung cancer susceptibility with an MspI restriction site polymorphism of the CYP1A1 gene was reported in our previous study. This polymorphism has been subsequently found to be closely linked to another isoleucine-valine (Ile-Val) polymorphism, which resulted in an Ile-Val amino acid replacement in the heme-binding region of P4501A1. We report here that genetic risk for squamous cell carcinoma of the lung was associated with these two polymorphisms of the CYP1A1 gene in terms of genotype frequencies and cigarette-smoking dose and that a more increased risk was observed for the individuals with "susceptible" genotypes of CYP1A1 combined with a deficient genotype of a mu-class glutathione S-transferase (GST1), which detoxifies the electrophilic metabolites of aromatic hydrocarbon procarcinogens activated by P4501A1. We first compared the total amounts of cigarettes consumed during a lifetime among 85 patients with squamous cell carcinoma of the lung, whose CYP1A1 and GST1 genes were identified. The patients with a susceptible homozygote of each of the MspI and Ile-Val polymorphisms contracted the carcinoma after smoking fewer cigarettes than those with other genotypes. When the GST1 polymorphism was taken into account, the cumulative cigarette amounts in combined genotyping of the two genes showed distinct differences, resulting in the lowest cigarette dose observed for the patients with a susceptible MspI or Ile-Val genotype of CYP1A1 combined with a deficient GST1 homozygote. Next, a case-control study revealed that the individuals with the susceptible MspI or Ile-Val genotype combined with deficient GST1 were at remarkably high risk with an odds ratio of 16.00 or 41.00, respectively (95% confidence interval, 3.76-68.02 or 8.68-193.61, respectively), at a low dose level of cigarette smoking.     

HLA antigens associated with susceptibility/resistance to HIV-1 infection

We studied the distribution of HLA-A, B, C, DR and DQ antigens in a cohort of HIV-1+ individuals and their heterosexual HIV seropositive (concordant) or seronegative (discordant) partners of Black non-Hispanic, Hispanic or Caucasian non-Hispanic ethnicity. The prevalence of DQ7 and Cw7 was significantly higher in the HIV-1+ compared to seronegative Black and Hispanic individuals, respectively. The frequency of DQ4 was significantly elevated in the Black seronegatives, whereas B53 was increased in the Hispanic seronegatives in comparison to the seropositives. No significant differences were observed between the Caucasian HIV infected and non-infected individuals. Analysis of the primary concordant HIV+ and discordant HIV+ individuals showed a marked increase in the prevalence of B44 in the Hispanic discordant seropositives, whereas the Caucasian primary concordants had a marked increase in the prevalence of A26. The prevalence of DQ7 and Cw7 was significantly increased in the Black and Hispanic secondary concordant seropositives, respectively in comparison to the seronegatives. The proportion of couples with matching HLA antigens was similar among the HIV-1+ concordant and discordant groups. These results provide additional evidence that HLA polymorphism may confer a genetic risk or protection for HIV-1 infection in individuals of various ethnic backgrounds.     

HLA-DRB1*08 influences the development of disease in Mexican Mestizo with spondyloarthropathy

OBJECTIVE: HLA class II encoded factors may influence the phenotype of ankylosing spondylitis (AS). These include HLA DRB1*07 for peripheral arthritis, and polymorphism of the HLA-linked LMP2 locus and HLA DRB1*08 for acute anterior uveitis (AAU). We studied the relationship between DRB1*08 and disease phenotype in additional populations of individuals with AS. METHODS: The patient population included 385 unrelated HLA-B27 positive individuals with AS. These included 204 Caucasians and 2 populations of Mexican Mestizo with AS: 106 with predominately adult onset disease from Guadalajara and 75 with predominately juvenile onset disease from Mexico City. The control population of 428 individuals included 210 random and 36 HLA-B27 positive unrelated Canadian Caucasians and 173 random and 9 HLA-B27 positive Mexican Mestizo from Mexico City. DRB1*08 typing was by sequence specific polymerase chain reaction. RESULTS: A significantly higher prevalence of DRB1*08 was observed in Mexican patients with juvenile onset disease (44.9%) and especially those with undifferentiated spondyloarthropathy (55.6%) compared to normal unrelated Mexican Mestizo (25.4%) (p < 0.01 for both) and in patients with undifferentiated spondyloarthropathy versus B27 controls (11.1%) (p = 0.03), although no significant differences were observed in within patient group comparisons based on phenotypic features of disease such as AAU and age at onset. No significant relationship between DRB1*08 and disease phenotype was evident in Caucasian individuals. CONCLUSION: Our data suggest DRB1*08 may influence the phenotype of spondyloarthritis in Mexican Mestizo, but do not support the view that DRB1*08 influences the development of AAU, as reported in a Japanese population.