线粒体827位点单核苷酸多态性与胆囊结石病易感性关系的研究

A study on relationship between mitochondrial DNA 827 locus SNP and cholecystolithiasis susceptibility

目的:研究线粒体单核苷酸多态性(SNPs)与胆囊结石病的关系,探讨导致胆囊结石病的可能易感因素。方法:对上海地区96个来自不同家系的胆囊结石病人和204名年龄<50岁且无胆囊结石的正常对照者进行线粒体DNACOX1基因、HVS1区和827位点序列检测;将测序结果与标准序列对比,以寻找存在的(SNPs),并比较各种SNP在两组之间的分布差异。结果:COX1基因6023G→A、6216T→C和6413T→C变异的分布在2组之间差异显著(P=0.036);线粒体第一高变区(HVS1)测序发现,16136C鄄16189C鄄16217C变异在2组之间差异显著(P=0.022);827位点序列检测发现827A→G在2组之间差异显著(P=0.000364)。结论:中国南方人群中,线粒体B4b单倍群个体(827A→G)易感胆囊结石病。

Objective To study the relationship between mitochondrial single nucleotide polymorphisms （SNPs） and cholecystolithlasis, and to find the potential predisposing factors leading to susceptibity to cholecystolithiasis. Methods Genomic DNA was extracted from whole blood samples of 96 patients from different cholecystolithiasis pedigrees and 204 unrelated non-gallstone-cartier controls; they are all Shanghai inhabitants. Mitochondrial DNA （mtDNA） cyclooxygenase 1（COX1）gene, hypervariantsl （HVS1） and 827 locus were chosen as target fragments and were amplified by polymerase chain reaction （PCR）. The purity of PCR products was testified by electrophoresis. The frequency of distribution of every SNP was compared between patients with cholecystolithiasis and those of the control group using Chi-square. Results The frequency of the variants 6023G→A,6216T→C and 6413T→C between the study group and the control group showed astatiotieally significant differen （6.25% vs 0. 9%, X^2= 5.12, P=0.036）; the frequency of the 16136C-16189C-16217C in HVS1, showed also difference between the 2 groups （8.33% vs 1.96%, X^2= 6.904, P=0.022）; the 16189C-16217C （in the study of B4 haplogroup, a common haplogroup in Asia）, the variant 827A→G showed the most evident difference between the 2 groups （12.50% vs 1.96%,X^2= 14.362, P=0.000364）. Conclusions In people living in Shanghai, who tend to be classified to the B4b haplogroup, those presenting 827A→G of mitochondrial DNA are predisposed to cholecystolithiasis.