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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

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          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/m 2, 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.

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          Most cited references42

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          Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults--study on optimal cut-off points of body mass index and waist circumference in Chinese adults.

          For prevention of obesity in Chinese population, it is necessary to define the optimal range of healthy weight and the appropriate cut-off points of BMI and waist circumference for Chinese adults. The Working Group on Obesity in China under the support of International Life Sciences Institute Focal point in China organized a meta-analysis on the relation between BMI, waist circumference and risk factors of related chronic diseases (e.g., high diabetes, diabetes mellitus, and lipoprotein disorders). 13 population studies in all met the criteria for enrollment, with data of 239,972 adults (20-70 year) surveyed in the 1990s. Data on waist circumference was available for 111,411 persons and data on serum lipids and glucose were available for more than 80,000. The study populations located in 21 provinces, municipalities and autonomous regions in mainland China as well as in Taiwan. Each enrolled study provided data according to a common protocol and uniform format. The Center for data management in Department of Epidemiology, Fu Wai Hospital was responsible for statistical analysis. The prevalence of hypertension, diabetes, dyslipidemia and clustering of risk factors all increased with increasing levels of BMI or waist circumference. BMI at 24 with best sensitivity and specificity for identification of the risk factors, was recommended as the cut-off point for overweight, BMI at 28 which may identify the risk factors with specificity around 90% was recommended as the cut-off point for obesity. Waist circumference beyond 85 cm for men and beyond 80 cm for women were recommended as the cut-off points for central obesity. Analysis of population attributable risk percent illustrated that reducing BMI to normal range ( or = 28) with drugs could prevent 15%-17% clustering of risk factors. The waist circumference controlled under 85 cm for men and under 80 cm for women, could prevent 47%-58% clustering of risk factors. According to these, a classification of overweight and obesity for Chinese adults is recommended.
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            Sex differences in lipid and lipoprotein metabolism: it's not just about sex hormones.

            It is commonly thought that sex hormones are important regulators of plasma lipid kinetics and are responsible for sexual dimorphism in the plasma lipid profile. Here we discuss the findings from studies evaluating lipid and lipoprotein kinetics in men and women in the context of what we know about the effects of exogenous sex hormone administration, and we conclude that it is more complicated than that. It has become clear that normal physiological alterations in the hormonal milieu (i.e. due to menopause or throughout the menstrual cycle) do not significantly affect plasma lipid homeostasis. Furthermore, parenterally administered estrogens have either no effect or only very small beneficial effects, whereas orally administered estrogens raise plasma triglyceride concentrations--a phenomenon that is not consistent with the observed sex differences and likely results from the hepatic "first-pass effect." The effects of progestogens and androgens mimic only in part the differences in plasma lipids between men and women. Thus, the underlying physiological modulators of plasma lipid metabolism responsible for the differences between men and women remain to be elucidated.
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              Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification.

              Methylenetetrahydrofolate reductase (MTHFR) catalyses the reduction of methylenetetrahydrofolate to methyltetrahydrofolate, a cofactor for homocysteine methylation to methionine. MTHFR deficiency, an autosomal recessive disorder, results in homocysteinemia. Using degenerate oligonucleotides based on porcine peptide sequence data, we isolated a 90-bp cDNA by PCR from pig liver RNA. This cDNA was used to isolate a human cDNA, the predicted amino acid sequence of which shows strong homology to porcine MTHFR and to bacterial metF genes. The human gene has been localized to chromosome 1p36.3. Two mutations were identified in MTHFR-deficient patients: a missense mutation (Arg to Gln), in a residue conserved in bacterial enzymes, and a nonsense mutation (Arg to Ter).
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                Author and article information

                Contributors
                zhixy90smile@126.com
                yangby23@mail.sysu.edu.cn
                fanfan0721ykl@163.com
                wangyanxun@genechina.com
                weijiantianjin@163.com
                qmzheng@mail.cmu.edu.cn
                +86 24 23261744 , gfsun@cmu.edu.cn
                Journal
                Lipids Health Dis
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central (London )
                1476-511X
                28 October 2016
                28 October 2016
                2016
                : 15
                : 185
                Affiliations
                [1 ]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
                [2 ]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
                [3 ]Division of Molecular Preventive Medicine, Shanghai Institute of Targeted Therapy and Molecular Medicine, Shanghai, 200433 China
                [4 ]Brain Disease Center, Tianjin Dagang Oil Field General Hospital, Tianjin, 300280 China
                Author information
                http://orcid.org/0000-0001-5135-7059
                Article
                354
                10.1186/s12944-016-0354-9
                5084372
                27793164
                2ea2c8ff-b54e-475b-9ce7-c00f44ab46df
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 17 June 2016
                : 16 October 2016
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Biochemistry
                mthfr c677t,mtrr a66g,overweight,obesity,lipid,interaction,gender-specificity
                Biochemistry
                mthfr c677t, mtrr a66g, overweight, obesity, lipid, interaction, gender-specificity

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