亚甲基四氢叶酸还原酶单核苷酸多态性与类风湿关节炎的相关性研究

目的检测我国南方汉族健康人群及类风湿关节炎（RA）患者亚甲基四氢叶酸还原酶（MTHFR）677C／T和1298A／C两个单核苷酸多态性的频率及遗传连锁关系，并分析两个单核苷酸多态性（SNPs）位点与RA的关系。方法研究对象共187人，其中健康对照组101人，RA患者86人，应用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）技术检测基因型和等位基因的分布频率，群体数理遗传学方法分析MTH-FRSNP的遗传平衡吻合度和相互间连锁不平衡关系。结果经Hardy-Weinberg检验，所研究的2个SNP位点各基因频率达到遗传平衡。677CC、CT、TT基因型在RA组中分别占36．0％、51．2％和12．8％，在对照组中分别为42．6％、44．6％和12．9％，两组频率分布无显著性差异（P〉0．05）。1298AA、AC、CC基因型在RA组中分别占60．5％、32．6％和7．0％，在对照组中分别为49．5％、46．5％和4．0％，分布无显著性差异（P〉0．05）。少见型677T等位基因在RA组和对照组分别为38．4％和35．1％，1298C在两组中分别为23．3％和27．2％，比较均未见差异。677C／T与1298A／C为强连锁不平衡关系。结论MTHFR677C／T和1298A／C与RA无明确关联。该人群中677C／T与1298A／C为强连锁不平衡关系。

Linkage study on methylenetetrahydrofolate reductase single nucleotide polymorphisms and methotrexate-related adverse effects in patients with rheumatoid arthritis

Objective To determine the allele and genotype frequencies of two single nucleotide polymor-phisms (SNPs) 677C/T,1298A/C in the methylenetetrahydrofolate reductase(MTHFR) gene in Chinese Southern Han individuals, and to assess whether there are differences in alleles frequencies among rheumatoid arthritis(RA) patients and normal controls. Methods 187 subjects(101 normal controls and 86 RA patients) were analyzed. The slide frequencies were carried out with polymerase chain reaction-restriction fragment langth polymorphism (PCR-RFLP). The two MTHFR SNPs Hardy-Weinberg equilibrium, linkage disequilibrium were analyzed with population genetics methods. Results The allele distribution of SNPs was in good unity with Hardy-Weinberg eqilibrium. The genotype frequencies of 677CC, CT, TT were 36.0%, 51.2%, 12.8%, respectively, in RA group, and 42.6%, 44.6% ,12.9%, respectively, in controls. The genotype frequencies of 1298AA,AC、CC were 60.5%、32.6%、 7.0%, respectively, in RA group, and 49.5% ,46.5% ,4.0% ,respectively, in controls. The frequencies of rarely allele 677T were 38. 4% and 35.1% in RA and controls. The 1298C were 23.3% and 27.2% in RA and controls. Allele frequencies were similar between RA group and controls, and there is no linkage between two SNPs and RA. The relationship between 677C/T and 1298A/C was strong linkage disequilibrium. Conclusions The research pro-vided Chinese southern Han population genetics data on MTHFR gene. The relationship between 677C/T and 1298A/C was strong linkage disequilibrium.