Investigation of gene-by-sex interactions for lipid traits in diverse populations from the population architecture using genomics and epidemiology study

Taylor, Kira C.; Carty, Cara L.; Dumitrescu, Logan; Bůžková, Petra; Cole, Shelley A.; Hindorff, Lucia A.; Schumacher, Fredrick; Wilkens, Lynne R.; Shohet, Ralph V.; Quibrera, P. Miguel; Johnson, Karen C.; Henderson, Brian E.; Haessler, Jeff; Franceschini, Nora; Eaton, Charles B.; Duggan, David; Cochran, Barbara; Cheng, Iona; Carlson, Chris; Brown-Gentry, Kristin; Anderson, Garnet L.; Ambite, José Luis; Haiman, Christopher A.; Marchand, Loı̈c Le; Kooperberg, Charles; Crawford, Dana C.; Buyske, Steven; North, Kari E.; Fornage, Myriam

doi:10.1186/1471-2156-14-33

Cited by 27 publications

(24 citation statements)

References 44 publications

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“…In addition, we also found that MTHFR 677TT genotype was associated with higher serum TG levels in females with overweight/obesity. Though heterogeneity by sex for lipid levels had been previously reported for other SNPs [33], the underlying mechanisms for the gender-specific association are unclear. It may be partly resulted from hormone action in combination with social and behavioral differences between men and women [29].…”

Section: Discussionmentioning

confidence: 99%

“…However, the underlying mechanism is unclear. Despite some advances in the identification of sex-specific genetic association with plasma lipid levels [11, 32, 33], few studies have explored the modifying effects of sex in the interactions between single nucleotide polymorphisms (SNPs) and overweight/obesity on lipid concentrations. Such exploration may provide valuable insight into the factors causing gender difference in the plasma lipid profile.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…A sex-stratified meta-analysis of lipid-related gene variants in European Americans has shown that rs28927680 and rs3135506 SNPs near the ZNF259 gene region had a sex specific effect on fasting TG levels. This effect was replicable in Mexican Americans/Hispanics 12. Another meta-analysis of GWAS on metabolic syndrome (MetS) has identified the rs2075290 SNP in the intronic region of ZNF259 as TG-related loci in European populations 13.…”

Section: Introductionmentioning

confidence: 87%

Sex-specific Association of the Zinc Finger Protein 259 rs2075290 Polymorphism and Serum Lipid Levels

Aung

Yin

et al. 2014

Int. J. Med. Sci.

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Background: Little is known about the association of ZNF259 rs2075290 single nucleotide polymorphism (SNP) and serum lipid levels in the Chinese population. This study aimed to detect the association of ZNF259 rs2075290 SNP and environmental factors with serum lipid levels between males and females in the Mulao and Han populations.Methods and Results: Genotyping of ZNF259 rs2075290 SNP was performed in 788 of Mulao and 778 of Han participants using polymerase chain reaction and restriction fragment length polymorphism. The genotype frequencies were significantly different between Mulao and Han populations (AA, 50.1% Vs 58.9%; AG, 42.3% Vs 35.7%; GG, 7.6% Vs 5.4%, P = 0.002) and between Han males and females (AA, 64.5% Vs 55.2%; AG, 28.3% Vs 40.6%; GG, 7.2% Vs 4.2%, P = 0.001). Serum levels of triglyceride (TG) in Mulao males, and total cholesterol (TC), TG and low-density lipoprotein cholesterol (LDL-C) in Mulao females were different between the AA and AG/GG genotypes (P < 0.05-0.001). Serum TC, LDL-C and apolipoprotein (Apo) A1 levels in Han males, and TG and ApoB levels and ApoA1/ApoB ratio in Han females were different between the AA and AG/GG genotypes (P < 0.05-0.001). An interaction between ZNF259 rs2075290 polymorphism and male gender on serum TC, LDL-C, and ApoA1 levels was noted in Han population (P < 0.05-0.01) but not in Mulao's.Conclusions: The subjects with AG/GG genotype in Mulao males and females and Han females have less favorable lipid profiles than those with AA genotype. In contrast, the subjects with AG/GG genotype in Han males have more favorable lipid profiles than those with AA genotype. These findings suggest that the association between ZNF259 rs2075290 SNP and serum lipid levels might have ethnic- and/or sex-specificity.

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“…Studying gene-by-environment (G×E) interactions is important, as it extends our 42 knowledge of the genetic architecture of complex traits and improves our understanding of the 43 underlying mechanisms of common diseases for novel and known loci (22)(23)(24). Several large-44 scale genome-wide G×E studies have successfully identified novel common variants accounting 45 for the environmental effects such as alcohol consumption and smoking status on lipid levels and 46 other CVD related traits (25)(26)(27)(28)(29)(30)(31)(32)(33)(34). These studies have successfully identified common variant loci 47 that were not detected via analysis of main effects alone.…”

Section: Introduction 29mentioning

confidence: 99%

Role of Rare and Low Frequency Variants in Gene-Alcohol Interactions on Plasma Lipid Levels

Wang

Chen

Bartz

et al. 2019

Preprint

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Investigation of gene-by-sex interactions for lipid traits in diverse populations from the population architecture using genomics and epidemiology study

Cited by 27 publications

References 44 publications

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

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

Sex-specific Association of the Zinc Finger Protein 259 rs2075290 Polymorphism and Serum Lipid Levels

Role of Rare and Low Frequency Variants in Gene-Alcohol Interactions on Plasma Lipid Levels

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