128例Ⅱ型糖尿病患者线粒体ND1基因突变位点的研究

Research on the mutation points of ND1 gene of mitochondrial DNA within 128 patients suffered type 2 diabetes mellitus

目的通过对128例Ⅱ型糖尿病(Type 2 diabetes mellitus,T2DM)患者线粒体DNA ND1基因进行突变位点筛查,探索ND1基因点突变与山西人群T2DM的相关性。方法 PCR扩增患者ND1基因所在区段,PCR产物直接测序分析。结果128例患者共有38例患者检测到基因点突变,突变检出率为29.7%。38例患者共筛出22个突变位点,2种突变类型。其中31例存在单个位点突变,5例存在2个位点突变,2例存在3个位点突变。22个突变位点中,3552(T→A)突变频率最高,为40.9%(9/22);3394(T→C)、3435(C→T)、3497(C→T)、3316(G→A)、3571(C→T)、3537(A→G)的突变频率分别为22.7%(5/22)、22.7%(5/22)、18.2%(4/22)、13.6%(3/22)、13.6%(3/22)和10.1%(2/22);其余突变位点的突变率均为4.5%(1/22)。在所有突变位点中,除3688(G→C)为异质性突变外,其余突变均为同质性。此外,22个突变位点中存在一个新的突变位点3499(A→T),属首次报道。结论 3552(T→A)和3394(T→C)突变频率最高,可能与山西地区T2DM发病相关;新发现的突变位点3499A→T(Thr→Ser),其致病性需要进一步研究。

Objective： To explore the association of ND1 gene mutation points of mitochondrial DNA and the patients suffered type 2 diabetes mellitus （T2DM） in Shanxi. Methods： Polymerase chain reaction and DNA sequencing were used to screen the mutations of ND1 gene. Results： 38 out of 128 patients were detected with the mutations of ND1 gene, the rate of which was 29. 7%. 22 mutation points and two kinds of mutations have been screened from 38 patients. Of all the patients, 31 of them have single mutation, 5 have two mutations, and the rest 2 cases have three mutations. Among these mutations, 3552 （T→A） mutation rate is 40. 9%, which is the highest mutation frequency; 3394 （T→C）, 3435 （C→T）, 3497 （C→T）, 3316 （G→A）, 3571 （C→T） and 3537 （A→G） mutation rate is 22.7% , 22. 7%, 18. 2%, 13.6%, 13.6% and 10. 1%, respectively; the remaining cases were 4. 5%. All of there mutations are homogeneity except for the mutation of the 3688 （G→C）, which is heterogeneity. In addition, a mutation 3499 （A→T） was newly discovered from all of the 22 mutations, which was the first report. Conclusion： 3552 （T→A） and 3394 （T→ C） have the highest mutation rate, which is assumed to be associated with T2DM in Shanxi; The newly discovered mutation points, 3499 A→T （Thr→Ser）, of which its pathogenesis needs to be studied deeply.