title: Gender-specific interactions of MTHFR C677T and MTRR A66G polymorphisms with overweight/obesity on serum lipid levels in a Chinese Han population.
abstract: BACKGROUND
  Little is known regarding the interactions of methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms with overweight/obesity on serum lipid profiles. The aim of the current study was to explore interactions between the two polymorphisms and overweight/obesity on four common lipid levels in a Chinese Han population and further to evaluate whether these interactions exhibit gender-specificity.
  
  
  METHODS
  A total of 2239 participants (750 females and 1489 males) were enrolled into this study. The genotypes of the MTHFR C677T and MTRR A66G were determined by a TaqMan assay. Overweight and obesity were defined as a body mass index between 24 and 27.99 and ≥ 28 kg/m2, respectively. The interactions were examined by factorial design covariance analysis, and further multiple comparisons were conducted by Bonferroni correction.
  
  
  RESULTS
  There was no significant difference in the genotypic and allelic frequencies between females and males (MTHFR 677 T allele: 54.47 % for females and 54.40 % for males; MTRR 66G allele: 24.73 % for females and 24.71 % for males). Interaction between the MTHFR C677T polymorphism and overweight/obesity on serum triglyceride levels, and interaction between the MTRR A66G polymorphism and overweight/obesity on serum high-density lipoprotein cholesterol levels were detected in women (P = 0.015 and P = 0.056, respectively). For female subjects with overweight/obesity, the serum triglyceride levels in MTHFR 677TT genotype [1.09 (0.78-1.50) mmol/L] were significantly higher as compared with MTHFR 677CC genotype [0.90 (0.60-1.15) mmol/L, P = 0.007], and the MTRR 66GG genotype carriers had higher serum high-density lipoprotein cholesterol levels than those with MTRR 66AG genotype (1.46 ± 0.50 vs. 1.19 ± 0.31 mmol/L, P = 0.058). Furthermore, in male subjects with overweight/obesity, the MTHFR 677CT genotype carriers had higher low-density lipoprotein cholesterol levels than those with MTHFR 677TT genotype (2.96 ± 1.07 vs. 2.74 ± 0.88 mmol/L, P = 0.015).
  
  
  CONCLUSIONS
  Our results indicate that there exist interactive effects of the MTHFR C677T and MTRR A66G polymorphisms with overweight/obesity on some lipid traits in Chinese Han population, and the effects were gender-specific.
authors: Research Center of Environment and Non-Communicable Disease, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, People's Republic of China.
authors: Xueyuan
authors: X
authors: Zhi
authors: Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Preventive Medicine, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China.
authors: Boyi
authors: B
authors: Yang
authors: Research Center of Environment and Non-Communicable Disease, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, People's Republic of China.
authors: Shujun
authors: S
authors: Fan
authors: Division of Molecular Preventive Medicine, Shanghai Institute of Targeted Therapy and Molecular Medicine, Shanghai, 200433, China.
authors: Yanxun
authors: Y
authors: Wang
authors: Brain Disease Center, Tianjin Dagang Oil Field General Hospital, Tianjin, 300280, China.
authors: Jian
authors: J
authors: Wei
authors: Research Center of Environment and Non-Communicable Disease, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, People's Republic of China.
authors: Quanmei
authors: Q
authors: Zheng
authors: Research Center of Environment and Non-Communicable Disease, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, People's Republic of China. gfsun@cmu.edu.cn.
authors: Guifan
authors: http://orcid.org/0000-0001-5135-7059
authors: G
authors: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D015992:Body Mass Index; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000097:blood / Q000235:genetics; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000235:genetics* / Q000473:pathology; D050177:Overweight / Q000097:blood / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide
chemical_list: D008055:Lipids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Gender-specificity; Interaction; Lipid; MTHFR C677T; MTRR A66G; Obesity; Overweight