PAX4基因多态性与胰岛自身抗体阴性酮症倾向糖尿病的关系  

PAX4 gene polymorphism and islet autoantibody-negative ketosis-prone diabetes

作　　者：周敏[1,2] 张英[1] 张冬梅[1,2] 林建[1] 王建平[1] 周海峰[1] 周智广[1] 

机构地区：[1]中南大学湘雅二医院代谢内分泌研究所,糖尿病中心,长沙410011 [2]中南大学湘雅医院内分泌科,长沙410008

出　　处：《中南大学学报（医学版）》2010年第3期215-221,共7页Journal of Central South University ：Medical Science

基　　金：国家“973”项目(2006CB503901);湖南省科技厅项目(06JF3210);湖南省卫生厅重点研究项目(A2004-004)~~

摘　　要：目的:探讨配对盒4(paired box4,PAX4)基因多态性与胰岛自身抗体阴性酮症倾向糖尿病(KPD)的关系。方法:应用变性高效液相色谱法(DHPLC)筛查141例谷氨酸脱羧酶自身抗体(GAD-Ab)和蛋白酪氨酸磷酸酶自身抗体(IA-2Ab)阴性的KPD患者(KPD组)和112例非糖尿病对照者(NC组)的PAX4基因外显子3和9,对异常峰型者经测序证实其碱基改变。应用聚合酶链反应-限制性长度多态性分析(PCR-RFLP)法对141例KPD患者和308例对照者的PAX4基因A1168C多态位点进行等位基因和基因型频率分析。结果:在本组人群中未发现PAX4基因外显子3有变异。外显子9中的单核苷酸多态性(SNP)位点A1168C,引起错义突变P321H(rs712701)。A1168C位点的C等位基因和CC基因型频率在KPD组与NC组间差异无统计学意义;按性别分层后,KPD组C等位基因和CC基因型频率差异均有统计学意义(P=0.009,0.028);以年龄分层后,<20岁组与≥20岁组比较C等位基因和CC基因型频率分布差异均有统计学意义(P=0.034,0.032);在CC基因型的KPD患者中,空腹C肽(FCP)水平高于AA基因型者,差异有统计学意义(P=0.005)。结论:本组中国南方汉族人群PAX4基因A1168C(P321H)多态性与胰岛自身抗体阴性KPD未见关联,但分层研究提示PAX4基因A1168C多态性对男性和<20岁的KPD患者的发病可能有影响。Objective To investigate PAX4 gene polymorphism and its association with islet autoantibody-negative patients with ketosis-prone diabetes in Chinese Han population.Methods We screened the variation of exon 3 and 9 within PAX4 gene by denaturing high performance liquid chromatography（DHPLC）in 112 non-diabetes control subjects（NC group）and 141 patients with ketosis-prone diabetes（KPD group）,who were both negative for glutamic acid decarboxylase antibody（GAD-Ab）as well as protein tyrosine phosphatase antibody（IA-2Ab）.The sequences of abnormal peaks were analyzed by DNA-sequencing.The A1168C single nucleotide polymorphism in PAX4 gene was genotyped using polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP）in 308 non-diabetic control subjects and 141 KPD patients.Results No variation was discovered in PAX4 gene exon 3 both in the patients and in the controls.There was a single nucleotide polymorphism locus A1168C in the PAX4 gene exon 9,which induced mis-sence mutation P321H（rs712701）.No significant difference was observed in the genotype and allele frequencies of A1168C polymorphism between KPD patients and control subjects（P=0.532,0.426）.The difference was detected in the CC genotype and C allele frequencies in the KPD group when patients were stratified by gender（P=0.009,0.028）.According to age at diagnosis,the difference was observed in the CC genotype and C allele frequencies between 20 years old and ≥20 years old in the KPD group（P=0.034,0.032）.The level of FCP in the CC genotype group was significantly higher than that of FCP in AA genotype group（P=0.005）.Conclusion A1168C polymorphism in PAX4 gene may not play an essential role in the genetic susceptibility of the islet autoantibody-negative KPD in Chinese Han population.However,A1168C variation may contribute to the predisposition to the male or 20 years old patients with islet autoantibody-negative KPD.

关 键 词：酮症倾向糖尿病 PAX4基因 单核苷酸多态性 变性高效液相色谱法 

分 类 号：R587.2[医药卫生—内分泌]