Methylenetetrahydrofolate Reductase Gene Polymorphism C677T is Associated with Increased Risk of Coronary Heart Disease in Chinese Type 2 Diabetic Patients.

Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus (T2DM). Previous researches report that methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms might influence the occurrence of coronary heart disease (CHD) in T2DM patients. The purpose of this study was to evaluate whether MTHFR C677T and A1298C mutations are associated with the risk of CHD in T2DM patients. Methods A total of 197 subjects with T2DM were studied, of which 95 patients with CHD. The genotypes of MTHFR C677T and A1298C were analyzed by using dideoxy chain-termination method, and compared between patients with CHD and those without CHD. Results We found that the frequency of the 677T allele was significantly higher in T2DM patients with CHD than those without CHD (P=0.011). However, there was no significant difference in any of the examined haplotypes between T2DM patients with and without CHD. Furthermore, the 677T allele was associated with a higher risk of CHD development in diabetic patients with lower homocysteine (Hcy) levels (≤15 µmol/L) (P=0.006), while no effect of MTHFR gene polymorphism on the incidence of CHD was found in patients with higher Hcy levels (>15 µmol/L) (P=0.491). Conclusion The MTHFR C677T gene polymorphism is associated with the risk of CHD of diabetic patients and could be used as an effective marker for CHD in Chinese diabetic populations with normal Hcy levels.

Association Between Homocysteine Level and Methylenetetrahydrofolate Reductase Gene Polymorphisms in Type 2 Diabetes Accompanied by Dyslipidemia.

Objective To investigate the association between total homocysteine (tHcy) level in plasma and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus (T2DM) accompanied by dyslipidemia. Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively. Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C. Plasma tHcy and lipid levels were measured as well. The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test. Plasma tHcy level of T2DM patients who carried the different genotypes was compared by Student's t test. Results Finally, 82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study. There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism in T2DM patients (t=2.27, P=0.02). Moreover, the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677 TT genotype was significantly higher than that in those with CT+CC genotype (13.62±6.97 vs. 10.95±3.62 µmol/L, t=2.20, P=0.03); while for patients without dyslipidemia, comparison of the tHcy level between those who carried the above two alleles showed no significantly difference (13.34±6.03 vs. 12.04±5.09 µmol/L, t=1.08, P=0.29). Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.

Pharmacogenetics of statins treatment: Efficacy and safety.

WHAT IS KNOWN AND OBJECTIVE: Statins are widely used worldwide in the prevention and treatment of coronary atherosclerotic heart disease and ischaemic stroke. However, in clinical application, statins have shown great individual differences in terms of the efficacy and safety, some of which are related to genetic factors. The purpose of this article was to summarize the recent advances about the correlation between gene polymorphisms and the efficacy/safety of statins. METHODS: We searched the databases including PharmGKB and PubMed (published before June 2019) using the keywords such as 'statin', 'gene polymorphism' and 'SNP' and obtained more than 100 articles. In this review, we described the clinical studies of genetic variants associated with both the efficacy and adverse reactions of statins. We also clarified the importance of taking pharmacogenetic variation into account to improve the clinical application of statins. RESULTS AND DISCUSSION: The available data were collected and analysed to present the polymorphisms of candidate genes encoding the most promising proteins including SLCO1B1 (encoding uptake transporters); ABCB1, ABCC2, ABCG2 (encoding effluent transporter); APOE, APOA5 (encoding apolipoprotein); genes encoding cytochrome P450 enzyme system; KIF6, HMGCR, LDLR, LPA, PCSK9, COQ2, CETP, etc These genes were proved to be related to the pharmacodynamics and pharmacokinetics of statins, thus affecting the efficacy and safety. WHAT IS NEW AND CONCLUSION: In this paper, the correlation between gene polymorphisms and the efficacy/safety of statins was summarized. The authors reached a consensus that the variants of the genes encoding uptake and effluent transporters have the most effect on the efficacy/safety of statins. It pointed out that it is desirable to do genetic testing of these transporter genes to reduce the incidence of myopathy or to achieve better outcomes before patients use statins, especially in the regions with high frequency of risk allele.