WITHDRAWN: Association of homocysteine-metabolizing enzyme gene polymorphisms and lipid profiles: an investigation of a geneenvironment interaction

Abstract

// Shanqun Jiang 1, 2, * , Scott A. Venners 3, * , Yi-Hsiang Hsu 4, 5 , Justin Weinstock 6 , Suwen Wu 1 , Yanfeng Zou 7 , Faming Pan 7 and Xiping Xu 2, 8 1 School of Life Sciences, Anhui University, Hefei, China 2 Institute of Biomedicine, Anhui Medical University, Hefei, China 3 Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada 4 Institute for Aging Research, HSL and Harvard Medical School, Boston, MA, USA 5 Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, Boston, MA, USA 6 Department of Statistics, University of Virginia, Charlottesville, VA, USA 7 Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China 8 Division of Epidemiology and Biostatistics, University of Illinois at Chicago School of Public Health, Chicago, IL, USA * These authors contributed equally to this work Correspondence to: Shanqun Jiang, email: shanqunjiang2014@163.com Keywords: MTHFR; MTR; polymorphism; lipid; interaction Received: September 11, 2017      Accepted: November 16, 2017      Published: January 04, 2018 ABSTRACT This cross-sectional study investigated the gene-environment interactions between the MTHFR and MTR polymorphisms and gender with regard to lipid profiles in a general Chinese population. We recruited 2,124 individuals from Anhui Province, China. The MTHFR (C677T and A1298C) and MTR (A2756G) polymorphisms were genotyped, and serum lipid levels, including TC, TG, LDL-C, and HDL-C, were determined. Our results showed that male MTR AG + GG genotype carriers had significantly lower serum TC (adjusted β ± [SE]:-0.25 ± 0.10 mmol/L; P = 0.0159), LDL-C (adjusted β ± [SE]:-0.24 ± 0.09 mmol/L; P = 0.0049), and HDL-C (adjusted β ± [SE]:-0.09 ± 0.03 mmol/L; P = 0.0055) levels than the AA carriers. Male MTHFR677TT genotype carriers had significantly higher serum TC (adjusted β±[SE]: 0.28 ± 0.13 mmol/L; P = 0.0287) and LDL-C (adjusted β ± [SE]: 0.26 ± 0.13 mmol/L; P = 0.0485) levels than CC + CT carriers. In subsequent analyses, there was a significant interaction between the MTR AG+GG genotypes and gender in association with TC, LDL-C and TG levels ( P = 0.0378, 0.0054 and 0.0183 for interaction, respectively).The interaction term for the MTHFR 677TT genotype and gender was also significant for TC and LDL-C levels ( P = 0.0147 and 0.0243 for interaction, respectively). Further haplotype analysis showed that there also were significant interactions between gender and hap2 (MTHFR 677C/1298A) on TC ( P = 0.009) and LDL-C ( P = 0.013). We suggest that the negative effects of the MTR and MTHFR genotypes on serum lipids are based on certain gene-environment interactions in the Chinese general population.