Association between MTHFR gene C677T polymorphism and gestational diabetes mellitus in Chinese population: a meta-analysis

Abstract

Background and purposeThe relationship of the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with the incidence of gestational diabetes mellitus (GDM) in the Chinese population remains controversial. This study aimed to further clarify the effect of the MTHFR gene C677T polymorphism on GDM risk among Chinese pregnant women based on current evidence.MethodsSeveral databases were searched up to July 29, 2023 for relevant case-control studies. The numbers of patients with and without the T allele of the MTHFR gene C677T polymorphism in the GDM and control groups were determined, and all statistical analyses were performed by RevMan 5.3 software and STATA 15.0 software. Trial sequential analysis (TSA) was performed by TSA version 0.9 beta software to determine the required information size.ResultsA total of 17 case-control studies involving 12345 Chinese participants were included. The pooled results demonstrated that the T allele of the MTHFR gene C677T polymorphism was significantly associated with an increased risk of GDM, which was manifested by the five gene models of the MTHFR C677T polymorphism [T vs. C: odds ratio (OR)=1.59, P=0.03; TT vs. CC: OR=2.24, P<0.001; TC vs. CC: OR=1.28, P=0.05; (TT+TC) vs. CC: OR=1.55, P=0.003; TT vs. (TC+CC): OR=1.89, P<0.001]. Subgroup analysis based on the regions indicated that the significant relationship between the T allele of the MTHFR gene C677T polymorphism and an increased risk of GDM was detected only among the southern population [T vs. C: OR=1.62, P=0.09; TT vs. CC: OR=2.22, P=0.004; TC vs. CC: OR=1.17, P=0.28; (TT+TC) vs. CC: OR=1.43, P=0.03; TT vs. (TC+CC): OR=1.97, P=0.006]. TSA plots showed that the information sizes for the association between the MTHFR gene C677T polymorphism and GDM risk were sufficient in the homozygote (TT vs. CC) and recessive (TT vs. TC+CC) models.ConclusionThe MTHFR gene C677T polymorphism is closely related to susceptibility to GDM in the southern Chinese population, and the C-T mutation serves as an important genetic risk factor for GDM. More well-designed large case-control studies are needed to further confirm the above findings.

More evidence for widespread antagonistic pleiotropy in polymorphic disease alleles

“…At position 677 of MTHFR there is a C/T SNP and individuals heterozygous or homozygous for the T nucleotide produce a MTHFR protein with reduced activity which leads to lower levels of folate and higher levels of homocysteine in the blood. Clinically, in addition to increased risks of a variety of birth defects from the presence of the T allele ( Pi et al, 2020 ), is also associated with higher risks of schizophrenia ( Lewis et al, 2005 ), male infertility ( Karimian and Colagar, 2016 ; Aliakbari et al, 2020 ), gestational diabetes ( Tan and Chen, 2023 ) and recurrent pregnancy loss ( Wu et al, 2012 ) in Asians, and Alzheimer’s disease in Asians ( Hua et al, 2011 ; Peng et al, 2014 ) and APOE4 carriers ( Peng et al, 2014 ). At position 1,298 of MTHFR there is an A/C SNP with a similar biochemical effect but where the effects of the C allele are generally less severe, but evidence shows an association with increased cervical cancer risk ( Yi et al, 2016 ) and reduced sperm counts in Asian ( Aliakbari et al, 2020 ), Moroccan ( Eloualid et al, 2012 ), and Indian ( Singh et al, 2010 ) populations.…”