Abstract 274: Preliminary Candidate Gene Analysis In The Women’S Interagency HIV Study Shows Pleiotropic Effect Of APOB4 And Novel Associations Of BMP4 And NOS3 With Metabolic Syndrome Traits.
Purpose: To evaluate associations between candidate genes that promote pro-vasoconstriction, pro-coagulating, and pro-inflammatory vascular environment which lead to the constellation of phenotypes known as Metabolic Syndrome.
Materials and Methods: 3788 women from the Women’s Interagency HIV Study were genotyped using and Illumina 5M array. Thirty two candidate genes were selected from a comprehensive literature search that promoted pro-vasoconstrictive, pro-coagulative and pro-inflammatory vascular environment. Also three genes (APOB, CETP, LPL) were selected to serve as positive control due to their established association evidence with Metabolic Syndrome and combination of Metabolic Syndrome components. Single SNP regression analysis was performed using the additive model, adjusting for age at baseline and BMI where appropriate. Nine principal components obtained from genome wide SNPs were added to the model to control for population structure. Phenotypes were derived using ATP III definition as a guideline. The baseline values of the phenotype were analyzed. 2000 SNPs were assayed within and 10kb upstream and downstream of each of the 32 gene, which results an experimental wide significance level 2.5e-05.
Results: Several previously reported SNPs in the APOB gene were marginally significant for HDL cholesterol and total cholesterol traits. Previously unreported SNP rs11687484 reached experimental wide significance for both hemoglobin A1C and fasting glucose. Eight SNPs in CETP reached experimental wide significance with HDL cholesterol, and nonHDL cholesterol/HDL cholesterol ratio phenotypes. A SNP rs72680532 in BMP4 gene is also significantly associated with total cholesterol/HDL cholesterol ratio. BMP4 gene has not been reported to be associated with any Metabolic Syndrome traits or cardiovascular disease. Previously unreported association between SNP rs3918229 in NOS3 gene and HDL cholesterol reached experimental wide significance.
Conclusion: Multiple genes are associated with traits contributed Metabolic Syndrome, which potentially suggests pleotropic effects.
Author Disclosures: Y. Natanzon: None. X. Zhu: None. N. Morris: None. A. Sharma: None. D. Gustafson: None. C. Liu: None. R. Greenblatt: None. L. Pearce: None. O. Adeyemi: None. R. Irvin: None. D. Dykxhoorn: None. I. Ofotokun: None. M. Floris-Moore: None. C. Pierce: None.
- © 2014 by American Heart Association, Inc.