The Influence of MTHFR C677T Variants on Neuropathy Risk Among T2dm Patients Receiving Monotherapy Metformin

Michael Resta Surya Yanuar, E. Istyastono, D. Virginia
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Abstract

Neuropathy is the most common microvascular complication among type 2 diabetes mellitus (T2DM). Metformin consumption increases neuropathy risk. The Methylenetetrahydrofolate reductase (MTHFR) enzyme has confirmed its role in neuropathy. Metformin and MTHFR could decrease folate and induce hyperhomoscysteine. One of the common variants of the MTHFR gene is C677T and its located in the exon area. This study aimed to observe the association between variant C677T in the MTHFR gene and the risk of neuropathy among newly diagnosed T2DM patients with naive metformin. This cross-sectional study recruited 103 patients. The neuropathy risk was examined according to medical judgment through Neuropathy Symptom Score (NSS) and Neuropathy Disability Score (NDS) criteria. Genotyping C677T was performed using PCR-RFLP. This study found only one patient has a homozygote mutant, but more than 50% of patients were detected with allele mutants. There were no statistical differences in patient characteristics between CC and CT genotypes (p>0.05). Association between C677T and neuropathy risk was not significant statistically, either in the genotype model (p=0.97), allele model (p=0.82), and dominant model (p=0.91). There was still no significant association after adjusting for several confounding factors. We conclude that C677T in our population did not influence neuropathy risk. More specific criteria and laboratory parameters indicated neuropathy should be examined in the future study. Keywords: MTHFR, neuropathy, metformin, and T2DM
接受二甲双胍单药治疗的 T2dm 患者中 MTHFR C677T 变异对神经病变风险的影响
神经病变是 2 型糖尿病(T2DM)中最常见的微血管并发症。服用二甲双胍会增加神经病变的风险。亚甲基四氢叶酸还原酶(MTHFR)已被证实在神经病变中发挥作用。二甲双胍和 MTHFR 可减少叶酸并诱发高半胱氨酸血症。MTHFR 基因的常见变异之一是 C677T,位于外显子区域。本研究旨在观察MTHFR基因变异体C677T与二甲双胍新诊断T2DM患者神经病变风险之间的关系。这项横断面研究共招募了 103 名患者。通过神经病变症状评分(NSS)和神经病变残疾评分(NDS)标准,根据医学判断对神经病变风险进行检查。使用 PCR-RFLP 对 C677T 进行基因分型。研究发现,只有一名患者存在同型突变,但超过 50% 的患者被检测出等位基因突变。CC 和 CT 基因型的患者特征没有统计学差异(P>0.05)。无论是在基因型模型(P=0.97)、等位基因模型(P=0.82)还是显性模型(P=0.91)中,C677T 与神经病变风险之间的关系均无显著统计学意义。在调整了几个混杂因素后,仍然没有明显的关联。我们的结论是,我们人群中的 C677T 并不影响神经病变风险。在未来的研究中,应该对神经病变的具体标准和实验室参数进行研究。关键词MTHFR、神经病变、二甲双胍和 T2DM
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