Are MTHFR C677T and MTRR A66G Polymorphisms Associated with Overweight/Obesity Risk?  From a Case-Control to a Meta-Analysis of 30,327 Subjects

Fan, Shujun; Yang, Bo‐Yi; Zhi, Xueyuan; He, Miao; Wang, Da; Wang, Yanxun; Wang, Yinuo; Wei, Jian; Zheng, Qi; Sun, Guifan

doi:10.3390/ijms160611849

Cited by 19 publications

(12 citation statements)

References 35 publications

(68 reference statements)

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“…Subsequently, another study suggested that MTHFR 677T allele had an elevated obesity risk with a 1.24-fold compared with MTHFR 677C allele in Indian children 30. Although a large number of studies have assessed the associations between MTHFR C677T and overweight/obesity, the results are controversial in different populations 9,11,25,26,28,30,33,46,60. Our previous study attempted to investigate the relationship between MTHFR C677T and obesity-related traits in a Chinese children population.…”

Section: Discussionmentioning

confidence: 99%

Plausible relationship between homocysteine and obesity risk via MTHFR gene: a meta-analysis of 38,317 individuals implementing Mendelian randomization

Fu¹,

Li²,

Luo³

et al. 2019

DMSO

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Objective Numerous studies have explored the role of methylenetetrahydrofolate reductase gene ( MTHFR ) C677T polymorphism and homocysteine (Hcy) concentration in obesity, but the results are inconsistent. Hence, we performed a meta-analysis implementing Mendelian randomization approach to test the assumption that the increased Hcy concentration is plausibly related to the elevated risk of obesity. Methods Eligible studies were selected based on several inclusion and exclusion criteria. Correlations between MTHFR C677T and obesity risk, MTHFR C677T and Hcy concentration in obesity, Hcy concentration, and obesity were estimated by ORs, effect size and standard mean difference with their corresponding 95% CIs, respectively. Furthermore, Mendelian randomization analysis was performed to estimate the relationship between Hcy level and obesity. Results Consequently, this meta-analysis implemented with Mendelian randomization approach was conducted among 8,622 cases and 29,695 controls. The results indicated that MTHFR C677T is associated with an increased risk of obesity (for T vs C: OR=1.06, 95% CI=1.02–1.10; for TT vs CC: OR=1.13, 95% CI=1.03–1.24). Moreover, in obese subjects, the pooled Hcy concentration in individuals of TT genotype was 2.91 mmol/L (95% CI: 0.27–5.55) higher than that in individuals of CC genotype. Furthermore, the pooled Hcy concentration in subjects with obesity was 0.74 mmol/L (95% CI: 0.36–1.12) higher than that in controls. The evaluated plausible OR associated with obesity was 1.23 for 5 μmol/L Hcy level increase. Conclusions Through this meta-analysis, we emphasize a strong relationship between Hcy level and obesity by virtue of MTHFR C677T polymorphism.

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Section: Discussionmentioning

confidence: 99%

Plausible relationship between homocysteine and obesity risk via MTHFR gene: a meta-analysis of 38,317 individuals implementing Mendelian randomization

Fu¹,

Li²,

Luo³

et al. 2019

DMSO

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“…Moreover, there are some data showing that obesity could also cause ER stress, which, in turn, results in inhibition of insulin receptor signaling through hyperactivation of JNK and subsequent serine phosphorylation of insulin receptor substrate-1 [45]. Although studies evaluating associations between HHcy and being overweight/obesity were inconsistent [46,47,48,49], a recent meta-analysis reported that neither the MTHFR C677T polymorphism nor the MTRR A66G polymorphism was found to be significantly associated with being overweight/obesity in Chinese Han population [50]. It is thus plausible to speculate that insulin resistance due to being overweight/obesity may be aggravated by exposure to HHcy.…”

Section: Discussionmentioning

confidence: 99%

Additive Interaction of MTHFR C677T and MTRR A66G Polymorphisms with Being Overweight/Obesity on the Risk of Type 2 Diabetes

Zhi

Yang

Fan

et al. 2016

IJERPH

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Although both methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms have been associated with type 2 diabetes (T2D), their interactions with being overweight/obesity on T2D risk remain unclear. To evaluate the associations of the two polymorphisms with T2D and their interactions with being overweight/obesity on T2D risk, a case-control study of 180 T2D patients and 350 healthy controls was conducted in northern China. Additive interaction was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S). After adjustments for age and gender, borderline significant associations of the MTHFR C677T and MTRR A66G polymorphisms with T2D were observed under recessive (OR = 1.43, 95% CI: 0.98–2.10) and dominant (OR = 1.43, 95% CI: 1.00–2.06) models, respectively. There was a significant interaction between the MTHFR 677TT genotype and being overweight/obesity on T2D risk (AP = 0.404, 95% CI: 0.047–0.761), in addition to the MTRR 66AG/GG genotypes (RERI = 1.703, 95% CI: 0.401–3.004; AP = 0.528, 95% CI: 0.223–0.834). Our findings suggest that individuals with the MTHFR 677TT or MTRR 66AG/GG genotypes are more susceptible to the detrimental effect of being overweight/obesity on T2D. Further large-scale studies are still needed to confirm our findings.

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“…In Mexico, in the most recent report by the National Survey of Health and Nutrition, the prevalence of overweight and obesity in people over the age of 20, adolescents, and children was 72.5%, 36.3% and 33.2%, respectively (3). Obesity is a multifactorial disease that involves environmental and genetic factors (4). Candidate genes associated with obesity include the methylenetetrahydrofolate reductase gene ( MTHFR ), located in 1p36.3, of which the rs1801133 polymorphism (677C>T; A222V) is the most common and majorly studied (5).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, the 677T allele has been linked with overweight/obesity risk, dyslipidemias, and diabetes in several populations. However, so far, the studies have been controversial (4, 5, 7, 8, 9, 10, 11, 12, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30). Here, we analyzed whether there is an association of the MTHFR 677C>T polymorphism with overweight and obesity, as well as its relationship with lipid profile, glucose level, and anthropometric measurements in a young Mexican population.…”

Section: Introductionmentioning

confidence: 99%

Association of the MTHFR 677C>T polymorphism with obesity and biochemical variables in a young population of Mexico

Leal-Ugarte

Peralta-Leal

Meza-Espinoza

et al. 2019

Journal of Medical Biochemistry

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Summary Background Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been associated with overweight people and obesity. The goal of this study was to investigate the relationship of the MTHFR 677C>T polymorphism with obesity and biochemical variables in young individuals of Mexico. Methods A total of 316 young individuals were included in the study, 172 with normal weight (NW) and 144 with over weight/obesity. Body mass index (BMI) was classified as NW, overweight, and obesity. Also, waist circumference was measured. Moreover, glucose, total cholesterol, and triglycerides were determined. Genotyping for MTHFR 677C>T polymorphism was performed by the PCR-RFLP method. Results There was no difference in the distribution of the MTHFR 677C>T polymorphism between individuals with NW and overweight/obesity; neither when they were divided by overweight vs NW, nor when we contrasted obese vs NW. However, an analysis stratified by gender showed a significant protector effect of the TT genotype against obesity in males and elevated waist circumference in females. Also, overweight/obese individuals with TT genotype had less risk of high cholesterol or triglycerides than overweight/obese subjects with the other genotypes. Conclusions These results suggest that the MTHFR 677T polymorphism might not be a risk factor for being overweight/obesity. Rather, on the basis of our results, this variant could be a protector effect. However, further large-scale population-based studies are still necessary to clarify the role of the MTHFR 677C>T polymorphism in overweight, obesity, and lipid profile level.

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Are MTHFR C677T and MTRR A66G Polymorphisms Associated with Overweight/Obesity Risk? From a Case-Control to a Meta-Analysis of 30,327 Subjects

Cited by 19 publications

References 35 publications

<p>Plausible relationship between homocysteine and obesity risk via <em>MTHFR</em> gene: a meta-analysis of 38,317 individuals implementing Mendelian randomization</p>

<p>Plausible relationship between homocysteine and obesity risk via <em>MTHFR</em> gene: a meta-analysis of 38,317 individuals implementing Mendelian randomization</p>

Additive Interaction of MTHFR C677T and MTRR A66G Polymorphisms with Being Overweight/Obesity on the Risk of Type 2 Diabetes

Association of the MTHFR 677C>T polymorphism with obesity and biochemical variables in a young population of Mexico

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