Association Of MTHFR C677T Polymorphisms With Diabetes Prevalence And New-onset Diabetes Among Chinese Hypertensive Patients

BackgroundDiabetes is a common chronic non-communicable disease.The burden of diabetes has become a heavy public health problem in China and the world.Meanwhile,hypertension is prevalent in China with the feature of high frequency of MTHFR 677TT genotype,low folic acid level and high homocysteine level.Hypertension with diabetes can lead to high risks of cardiovascular and cerebrovascular disease.Due to the insidious onset of diabetes that β-cell dysfunction commences prior to diagnosis of diabetes,early identification of high-risk factors can provide better prevention and cure methods in medical practice.Previous studies suggested that MTHFR C677T polymorphisms may be related to metabolic diseases including diabetes.However,the results were inconsistent.To date,the association between MTHFR C677T gene polymorphisms and diabetes in hypertensive patients remains unclear.ObjectiveWe aimed to evaluate the association of MTHFR C677T polymorphisms with the prevalence of diabetes and the risk of new-onset diabetes,and to examine any possible effect modifiers among hypertensive patients.MethodsThe current study was a post hoc analysis of the CSPPT(China Stroke Primary Prevention Trial).Briefly,CSPPT was a multi-community,randomized,double-blind,clinical controlled trial conducted from May 2008 to August 2013,which enrolled a total of 20,702 hypertensive patients without stroke or cardiovascular disease in China.Our paper consists of two parts.First,A total of 20,341 patients at baseline of CSPPT were included to investigate the association between MTHFR C677T gene polymorphisms and the prevalence of diabetes.Diabetes was defined as fasting plasma glucose(FPG)≥7.0 mmol/L or self-reported physician-diagnosed diabetes or the use of glucose-lowering drugs at baseline.Second,a total of 14,978 hypertensive adults without diabetes at baseline were included to examine the prospective association between MTHFR C677T polymorphisms and risk of new-onset diabetes.New-onset diabetes was defined as fasting plasma glucose(FPG)≥7.0 mmol/L at the exit visit or self-reported physician-diagnosed diabetes or the use of glucose-lowering drugs during follow-up.ResultsIn the cross-sectional study,the frequency of MTHFR C677T polymorphisms was 27.4%for CC,49.1%for CT,and 23.5%for TT genotypes.The prevalence of diabetes in participants with MTHFR 677 CC,CT and TT genotype was 10.0%,11.0%and 13.3%,respectively.Compared with participants with the CC/CT genotypes,those with TT genotype had a significant higher prevalence of diabetes(adjusted OR:1.33,95%CI:1.19-1.48).The stratified analyses showed that estimated glomerular filtration rate(estimated GFR,eGFR)(<90 vs.≥90 mL/min/1.73m2;P for interaction=0.007)and total homocysteine(tHcy)(<12.5(median)vs.≥12.5μmol;P for interaction=0.040)may modify the effect of TT(vs.CC/CT)genotype on diabetes prevalence.The stronger effect was found in participants with higher eGFR≥90 mL/min/1.73m2(adjusted OR:1.55;95%CI:1.36-1.77)or lower tHcy<12.5μmol(adjusted OR:1.57;95%CI:1.33-1.86)levels.In the prospective study,during a median follow-up of 4.5 years(interquartile range,4.2-4.7 years),the incidence rates of new-onset diabetes for participants with MTHFR 677 CC,CT and TT genotype was 10.6%,10.5%,and 11.9%,respectively.Consistently,a significant higher risk of new-onset diabetes(adjusted OR:1.18,95%CI:1.03-1.35)was observed in participants with MTHFR 677TT genotype,compared to those with CC/CT genotypes.The stratified analyses showed that fasting plasma glucose(<6.1 vs.≥6.1mmol/L;P for interaction=0.043)and tHcy(<12.5(median)vs.≥12.5μmol;P for interaction=0.040)may modify the effect of TT(vs.CC/CT)genotype on new-onset diabetes.The stronger effect was found in participants with lower FPG<6.1mmol/L(adjusted OR:1.31;95%CI:1.11-1.53)or lower tHcy<12.5 μmol(adjusted OR:1.39;95%CI:1.13-1.71)levels.ConclusionsAmong Chinese hypertensive patients,compared to those with MTHFR 677 CC/CT genotypes,participants with 677TT genotype had a significantly higher prevalence of diabetes,as well as an increased risk of new-onset diabetes.