育龄妇女亚甲基四氢叶酸还原酶~MTHFR基因C677T，A1298C位点多态性与HR-HPV感染的相关性研究

目的　探讨育龄妇女亚甲基四氢叶酸还原酶（MTHFR）C677T,A1298C基因多态性与高危型人乳头瘤病毒（HR-HPV）感染的相关性。方法　收集2017年11月～2019年12月期间来天津市宝坻区人民医院孕检的育龄妇女所做HR-HPV及 MTHFR 多态性（包括C677T和A1298C）检测的样本资料共1 130例,比较MTHFR各代谢型之间HR-HPV的阳性率。结果　在MTHFR的三种代谢型中,弱代谢型是HR-HPV优势型别52型（χ2=4.764,P=0.029,OR=1.771,95%CI:1.054~2.975）、16型（χ2=4.304,P=0.038,OR=1.922,95%CI:1.027~3.599）及多重感染（χ2=3.985,P=0.046,OR=1.479,95%CI:1.005~2.176）的易感型别。结论　MTHFR 代谢活性受C677T和A1298C位点基因的双重影响,其中的弱代谢型是HR-HPV优势型别52型和16型,以及多重感染的易感型别。     

Methylenetetrahydrofolate reductase C677T gene polymorphism and the association with dyslipidemia in type 2 diabetic Palestinian patients

BackgroundDyslipidemia in diabetes is common and characterized by hypertriglyceridemia with decreased levels of high‐density lipoprotein. The objective of this study was to assess the prevalence of MTHFR C677T polymorphism in Palestinian T2DM patients and to investigate the association between this polymorphism and lipid profile in diabetic patients with and without dyslipidemia.MethodsA total of 208 T2DM patients including 98 with dyslipidemia and 110 without dyslipidemia were enrolled in this study. The MTHFR C677T genotyping was conducted by PCR‐RFLP followed by agarose gel electrophoresis.ResultsThere were no significant differences in either the genotype distribution or allele frequency in T2DM patients with or without dyslipidemia (37.8% CC, 54% CT, 8.2% TT vs. 48.2% CC, 41.8% CT, 11% TT; p = 0.209). However, among the dyslipidemic group, the TT carriers have a higher HDL level (46.8 ± 17.8) compared to (CC+CT) carriers (34.68 + 11.9) (p = 0.01). In the group without dyslipidemia, there was a significant elevation in diastolic blood pressure (DBP) among the CC carriers (83.6 ± 10.6) compared to those who carried at least one mutant allele (CT+TT) (78.1 ± 11.1) (p = 0.009).ConclusionsThe study shows that in our Palestinian population the MTHFR 677TT genotype lowers DBP significantly in patients without dyslipidemia and is related to increased level of HDL in diabetic dyslipidemia patients.     

亚甲基四氢叶酸还原酶C677T基因多态性与2型糖尿病合并冠心病的关系

目的 研究同型半胱氨酸代谢关键酶亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase,MTHFR）基因C677T多态性与糖尿病合并冠心病发病的关系,探讨MTHFR是否为糖尿病合并冠心病的易感基因。方法 研究对象包括105名糖尿病合并冠心病的患者（合并组）、88名单纯糖尿病患者（糖尿病组）和91名健康人。应用聚合酶链反应-限制性内切酶长度多态性方法（PCR—RFLP）检测MTHFR C677T基因多态性,同时检测血浆同型半胱氨酸（homocysteine,Hcy）、叶酸、维生素B12、各种血脂。结果 合并组与糖尿病组比,等位基因频率差异有统计学意义（Х^2=6．8,P〈0．05）,合并组T等位基因的OR值为1．638（95％ CI,1．082～2．479）,基因型频率差异亦有统计学意义（Х^2=5．481,P〈0．05）。Logistic回归分析显示MTHFR 677携带T基因（CT＋TT）的OR值为2．68（95％ CI,1．233—5．824）。结论 MTHFR 677携带T基因与2型糖尿病合并冠心病发生独立相关。检测MTHFR 677位点基因特点可能为糖尿病合并冠心病的预防以及个体化治疗提供新思路、新方法。     

适龄期孕妇复发性流产与亚甲基四氢叶酸还原酶、纤溶酶原激活物抑制物1基因多态性及血清叶酸浓度关系的研究

目的:探讨适龄期妇女复发性流产（recurrent spontaneous abortion, RSA）与叶酸代谢基因亚甲基四氢叶酸还原酶（methylene Tetrahydrofolate Reductase, MTHFR）、纤溶酶原激活物抑制物1（plasminogen activator inhibitor-1...     

Association of the methylenetetrahydrofolate reductase (MTHFR) gene variant C677T with serum homocysteine levels and the severity of ischaemic stroke: a case–control study in the southwest of China

ObjectiveTo determine whether the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism is linked to the risk of ischaemic stroke and circulating homocysteine (Hcy) levels in a Chinese population.MethodsThis case–control study recruited angiogram-diagnosed patients with ischaemic stroke and healthy control subjects. The plasma Hcy concentrations were measured and the MTHFR C677T gene polymorphism was genotyped. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of the ischaemic stroke.ResultsThis study recruited 198 patients with ischaemic stroke and 168 controls. The TT genotype conferred a higher risk for ischaemic stroke than the CC genotype (odds ratio of 3.563; 95% confidence interval [CI] 1.412, 4.350). The T allele was the predisposing allele for ischaemic stroke. Hcy had an area under the receiver operating characteristic (ROC) curve of 0.624 (95% CI 0.530, 0.758). The ROC for Hcy demonstrated its usefulness in predicting ischaemic stroke. Hcy levels were not associated with ischaemic stroke severity as measured by the NIHSS.ConclusionThe MTHFR C677T gene polymorphism affects circulating Hcy levels. The MTHFR C677T gene polymorphism and hyperhomocysteinaemia may play important roles in predicting the risk of ischaemic stroke.     

COVID‐19 spreading across world correlates with C677T allele of the methylenetetrahydrofolate reductase (MTHFR) gene prevalence

BackgroundHomocysteine assessment has been proposed as a potential predictive biomarker for the severity of COVID‐19 infection. The purpose of this review was to analyze the correlation between the prevalence of MTHFR C677 T gene polymorphism and COVID‐19 incidence and mortality worldwide.MethodsData regarding MTHFR C677 T gene mutation were obtained from the interrogation of the Genome Aggregation Database (genomAD), which is publicly available from the web“https://gnomad.broadinstitute.org.” COVID‐19 cases, including prevalence and mortality, were obtained from“https://www.worldometers.info/coronavirus” 27 August 2020.ResultsThere is a clear trend toward the worldwide prevalence of MTHFR 677 T and COVID‐19 incidence and mortality. The prevalence of MTHFR 677 T allele in the Latino population, and the incidence and mortality for COVID‐19 was higher for this ethnic group than that reported for most other populations globally. Statistical analysis showed a relatively strong correlation between C677 T and death from coronavirus.ConclusionsGenetic polymorphism of MTHFR C677 T may modulate the incidence and severity of COVID‐19 pandemic infection.     

Comparison of linkage disequilibrium patterns and haplotype structure of eight single nucleotide polymorphisms across the CYP1A2 gene between the Korean, and other populations registered in the International HapMap database

Background and objective: The aim of this study was to determine the frequencies of CYP1A2 gene polymorphisms, analyze Linkage disequilibrium (LD) blocks and haplotypes in a Korean population, and compare them with those in African, European, Japanese and Chinese populations. Methods: We searched across diverse studies conducted in Korea and the Knowledge Base for Korean Pharmacogenomics Research Network operated by Seoul National University to determine the frequency of single nucleotide polymorphisms (SNPs) of the CYP1A2 gene and to choose frequently occurring SNPs in a Korean population. We analyzed and confirmed the frequencies of CYP1A2 SNPs that are inferred as MAF >0·05 in 400 healthy Korean subjects, using direct sequencing and a TaqMan assay. The LD block and haplotypes were constructed from the SNP databases in the other races registered in the International HapMap (Europeans, Chinese, Japanese and Africans) and the haplotype frequencies in each race were compared with those in the Korean population. Results and discussion: We found 12 SNPs with minor allele frequency (MAF) values above 5% in the 5′ regulatory regions, the exon, and surrounding introns of CYP1A2 gene based on previous reports in Koreans. In this study, two of twelve SNPs were lower than 5% in frequency (n = 400). The CYP1A2 haplotypes were analyzed based on 10 SNPs, confirmed to have MAF >0·05 in this study. Four haplotypes (H1, H2, H3 and H4) represented most of the Korean population (>94%). Conclusions: The haplotype frequencies among the five ethnic groups revealed that haplotype distributions in Koreans were similar to those of the Japanese and Chinese, but were quite different to those of the Africans and Europeans. These LD and haplotype data should be useful in drug development and in understanding genetic associations of CYP1A2 with adverse drug effects. These inter‐ethnic differences in frequencies of SNPs and haplotypes may help to explain inconsistencies that have been reported in association studies and could contribute to predict the pharmacokinetics and pharmacodynamics of drugs that are metabolized by CYP1A2.