CTLA-4基因的多态性与宁夏儿童1型糖尿病的相关性研究

目的 探讨宁夏儿童1型糖尿病（IDDM）易感基因的多态性.方法 采用捕获-再捕获方法及病例对照的研究方法,回顾调查宁夏区、市、县级51所医院167所幼儿园、2816所小学、446所中学、22所职业中学的0～15岁34例IDDM初患病儿,选择IDDM患儿居住地附近71例0～15岁健康儿童作为对照,采用聚合酶链反应-限制性内切酶片段长度多态性（PCR-RFLP）技术测定CTLA-4相关基因的两个多态性等位基因位点;运用遗传连锁不平衡（TDT）方法筛选IDDM发生的易感基因的位点.结果 IDDM组与对照组之间CTLA-4基因SNP49（A/G）的等位基因A、G,差异有统计学意义（P＜0.05）;SNP-318（C/T）的等位基因C、T,无统计学意义（P＞0.05）;AG＋CT基因型、非AG＋CT基因型,差异有统计学意义（P＜0.05）.14例家系分析,父母携带GG基因型与AA基因型相比,其子女患病率明显增高,差异有统计学意义（P＜0.05）.结论 CTLA-4基因的多态性SNP49（A/G）等位基因、AG＋CT基因型的连锁与本地区IDDM的发生有关,其中携带GG基因型的父母其子女患IDDM的风险性增高.

An Analysis on Susceptible Genes Polymorphism of Insulin Dependent Diabetes Mellitus in Children in Ningxia

Objective To explore susceptible genes polymorphism of insulin dependent diabetes mellitus(IDDM) in children in Ningxia.Methods We retrospectively studied newly diagnosed cases of IDDM at age of 0-15 years old that recruited from 51 county-level or above hospitals and 167 kindergartens,2816 primary schools,446 second schools,22 occupation second schools in Ningxia area by the "Capture-Recapture" method and control group were selected from healthy children that lived nearby the areas in which the IDDM cases lived according to 1:2 matched principle.We used the polymerase chain reaction(PCR) and the restriction fragment length polymorphism(-RFLP) to analyze genotype frequencies of single nucleotide polymorphism(SNP)49G/A and SNP-318C/T of cytotoxic T lymphocyte antigen-4 gene(CTLA-4) between IDDM group and control group,and used combined transmission/ disequilibrium test(TDT) to ascertain the association of between the two candidate genes and IDDM in the population.Results The significant difference in the frequency of the SNP49A/G alleles of cytotoxic T lymphocyte associated-4(CTLA-4) gene was found between IDDM group and control group(P<0.05).But no significance was found for SNP-318C/T of the CTLA-4 gene(P>0.05).A significant difference in the frequency of the AG-CT genotype between AG+CT and no AG+CT(P<0.05)was observed.TDT analysis showed the patients who carried GG type alleles were of higher risk than them who carried AA type alleles(P<0.05) in 14 cases families.Conclusion The SNP 49A/G polymorphism in CTLA-4 gene had close relation with IDDM in Ningxia population.The patients who carried GG type alleles had higher risk of IDDM.