Gender-specific interactions of MTHFR C677T and MTRR A66G polymorphisms with overweight/obesity on serum lipid levels in a Chinese Han population

Abstract

BackgroundLittle 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.MethodsA 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.ResultsThere 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).ConclusionsOur 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.

Gene-environment interactions due to quantile-specific heritability of triglyceride and VLDL concentrations

“…Zhi et al reported that differences between the CC, CT, and TT genotypes of the MTHFR C677T polymorphism were significantly greater (P = 0.02) in women with BMI > 24 kg/m 2 (0.90, 0.99, 1.09 mmol/L, respectively) who had higher average triglycerides (1.00 mmol/L), than in leaner women (0.65, 0.71, 0.63 mmol/L, respectively) who had low triglycerides (0.67 mmol/L) 47 . Our analyses of Yin et al 's data (their Fig.…”

“…Gene-weight interactions have also been reported for individual SNPs, including those associated with APOA5 26,[32][33][34] , LPL 26,[35][36][37][38][39][40][41][42][43] , GCKR 26,44 , insulin receptor substrate-1 (IRS-1) 45,46 , methylenetetrahydrofolate reductase (MTHFR) 47,48 , proprotein convertase subtilisin/kexin type 9 (PCSK9) 48 , APOB 49 , APOE 50 , peroxisome proliferator-activated receptor γ 2 (PPARγ2) 51 , and patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) 52 .…”

“…Environmental factors that distinguish higher vs. lower triglycerides (e.g., obesity, physical inactivity, smoking, alcohol, high-carbohydrate diets, T2DM) are predicted to produce different genetic estimates under quantile-dependent expressivity. Traditionally, these differences have been attributed to gene-environment interactions, where: 1) the effect of the genotype on the phenotype differs by environment [26][27][28][29][30][31][32][33][34][35][36][37][41][42][43][45][46][47][48][49][50][51][52][53][54][55][58][59][60][61][62][63][65][66][67][74][75][76][77][78][79][80] , or equivalently: 2) the effect of the environment on the phenotype differs by genotype 36,[38][39][40]44,…”

The relationship between gene polymorphism of MTRR A66G and lower extremity deep venous thrombosis

“…Polymorphism refers to there may be more than two genotypes in the same genetic locus in random mating population. For this population, there are differences in the nucleotide sequence of individual genes called genetic polymorphism [21]. This kind of polymorphism can be divided into two categories, the polymorphism of DNA site and DNA length polymorphism [22,23].…”

Medical cost savings in Sakado City and worldwide achieved by preventing disease by folic acid fortification

“…The frequency of the T allele of MTHFR is 36.9%, 41.7%, 58.6% and 8.1%, in Japan, the USA, Mexico and Indonesia, respectively (Sadewa et al 2002). The authors also tested the following high frequency SNPs affecting folate and homocysteine metabolism (Hiraoka et al 2004): MTHFR A1298C, CBS844ins68 (cystathionine‐β‐synthase), MS A2756G (methionine synthase) (Cai et al 2014), MTRR A66G (methionine synthase reductase) (Zhi et al 2016), and RFC‐1 G80A (reduced folate carrier‐1) (Li et al 2016a). CBS844ins68 is the 8th exon insertion mutation and comprises 68 base pairs (Cai et al 2014).…”