The HMG-CoA Reductase Gene and Lipid and Lipoprotein Levels: the Multi-Ethnic Study of Atherosclerosis |
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Authors: | Yi-Chun Chen Yii-Der I Chen Xiaohui Li Wendy Post David Herrington Joseph F Polak Jerome I Rotter Kent D Taylor |
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Affiliation: | (1) Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA;(2) Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang-Gung University, Taipei, Taiwan;(3) Division of Cardiology, Department of Medicine, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA;(4) Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA;(5) Department of Internal Medicine/Cardiology, Wake Forest University Health Sciences, Winston-Salem, NC, USA;(6) Department of Radiology, Tufts-New England Medical Center, Boston, MA, USA;(7) Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, 333, Kueishan, Taoyuan, Taiwan |
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Abstract: | HMG-CoA reductase (HMGCR) is an enzyme involved in cholesterol synthesis. To investigate the contribution of the HMGCR gene to lipids and lipoprotein subfractions in different ethnicities, we performed an association study in the Multi-Ethnic
Study of Atherosclerosis (MESA). In total, 2,444 MESA subjects 597 African-Americans (AA), 627 Chinese-Americans (CHA), 612
European-Americans (EA), and 608 Hispanic-Americans (HA)] without statin use were included. Participants had measurements
of blood pressure, anthropometry, and fasting blood samples. Subjects were genotyped for 10 single nucleotide polymorphisms
(SNPs). After excluding SNPs with minor allele frequency <5%, a single block was constructed. The most frequent haplotype
was H1 (41–56%) in all ethnic groups except AA (H2a, 44.9%). Lower triglyceride level was associated with the H2a haplotype
in AA and H2 in HA. In HA, H4 carriers had higher levels of triglyceride and small low-density lipoprotein (s-LDL), and lower
high-density lipoprotein cholesterol (HDL-c), while carriers with H7 or H8 had associations with these traits in the opposite
direction. No significant association was discovered in both CHA and EA. The total variation for triglyceride that could be
explained by H2 alone was 2.6% in HA and 1.4% in AA. In conclusion, HMGCR gene variation is associated with multiple lipid/lipoprotein traits, especially with triglyceride, s-LDL, and HDL-c. The
impact of the genetic variance is modest and differs greatly among ethnicities. |
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Keywords: | Hydroxymethylglutaryl CoA reductases Association study Cholesterol Triglyceride Low-density lipoprotein size |
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