TY - JOUR
T1 - The HMG-CoA Reductase gene and lipid and lipoprotein levels
T2 - The multi-ethnic study of atherosclerosis
AU - Chen, Yi Chun
AU - Chen, Yii Der I.
AU - Li, Xiaohui
AU - Post, Wendy
AU - Herrington, David
AU - Polak, Joseph F.
AU - Rotter, Jerome I.
AU - Taylor, Kent D.
N1 - Funding Information:
Acknowledgments This research was supported by contracts N01-HC-95159 through N01-HC-95169 (MESA), RO1HL071205 (MESA family), and HL069757 (PARC) from the NHLBI. We thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org.
PY - 2009/8
Y1 - 2009/8
N2 - 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.
AB - 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.
KW - Association study
KW - Cholesterol
KW - Hydroxymethylglutaryl CoA reductases
KW - Low-density lipoprotein size
KW - Triglyceride
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U2 - 10.1007/s11745-009-3314-6
DO - 10.1007/s11745-009-3314-6
M3 - Article
C2 - 19554360
AN - SCOPUS:68349083490
SN - 0024-4201
VL - 44
SP - 733
EP - 743
JO - Lipids
JF - Lipids
IS - 8
ER -