【摘 要】
：
2型糖尿病(T2DM)是遗传异质性较高的多基因遗传病.通过全基因组关联研究技术发现内向整流钾通道蛋白J亚单位11(KCNJ11)基因与T2DM发生高度相关.KCNJ11基因变异可导致Kir6.2结构改变,引起KATP通道调节失控而导致胰岛素分泌紊乱,诱发T2DM发生.目的:探讨KCNJ11基因与延边朝鲜族和汉族人群T2DM发生的相关性.方法:利用SnaPshot单碱基延伸技术检测KCNJ11基因5
【机 构】
：
延边大学医学院医学遗传学教研室,吉林延吉133002 延边大学临床医学院体检科,吉林延吉13300
【出 处】
：
中国遗传学会第九次全国会员代表大会暨学术研讨会
论文部分内容阅读
2型糖尿病(T2DM)是遗传异质性较高的多基因遗传病.通过全基因组关联研究技术发现内向整流钾通道蛋白J亚单位11(KCNJ11)基因与T2DM发生高度相关.KCNJ11基因变异可导致Kir6.2结构改变,引起KATP通道调节失控而导致胰岛素分泌紊乱,诱发T2DM发生.目的:探讨KCNJ11基因与延边朝鲜族和汉族人群T2DM发生的相关性.方法:利用SnaPshot单碱基延伸技术检测KCNJ11基因5个SNPs(rs5218、rs5219、rs5215、R221C、rs1800854)的基因型.共检测了828例,其中朝鲜族480(T2DM患者157,T2DM合并EH(合并EH)患者142,NGT组181),汉族348(T2DM患者129,合并EH患者79,NGT组140),检测身高、体重、腰围、臀围、血压、体质指数(BMI)、TC、TG、HDL-C、LDL-C、FPG、血清脂连素(PA)和胰岛素(INS)水平.结果:1.KCNJ11基因5个SNPs等位基因频在朝鲜族人群NGT组:T2DM组:合并EH组分布为:rs5218(T)0.376:0.420:0.426;rs5219(T)0.414:0.366:0.398;rs5215(C)0.414:0.369:0.398;R221C(A)0.105:0.127:0.004;rs1800854(A)0.006:0.000.0.007;在汉族人群NGT组:T2DM组:合并EH组分布为:rs5218(T)0.464:0.465:0.456;rs5219(T)0.425:0.388:0.405;rs5215(C)0.425:0.388:0.405;221C(A)0.114:0.062:0.006;rs1800854(A)0.007:0.012:0.000;以上5个位点的等位基因频率均符合Hardy-Weinberg平衡定律(p＞0.05).2.延边汉族rs5218(T)等位基因频显著高于朝鲜族(p=0.023),其余4个位点均未发现朝汉族间民族差异(p＞0.05).3.在朝鲜族人群合并EH患者携带R221C(A)的CA基因型频率显著低于NGT组(0.7％vS.21.0％),降低罹患合并EH风险为0.027倍[p=2.84e-008,OR=0.027(95％CI:0.004-0.197)];在汉族T2DM患者携带R221C(A)的CA基因型频率显著低于NGT组(12.4％VS.22.9％),降低罹患T2DM风险为0.478倍[p=0.025,OR=0.478(95％CI:0.248-0.920)],在汉族合并EH患者携带R221C(A)的CA基因型频率显著低于NGT组(1.30％VS.22.9％),降低罹患T2DM合并EH风险为0.043倍[p=1.82e-005,0R=0.043(95％CI:0.006-0.323)].4.rs5219与rs5215存在完美连锁不平衡(D=1.000,r2=1.000).5.在朝鲜族NGT组中携带R221C的CA基因型个体(未发现AA基因型)比CC基因型个体BMI、WHR、FPG和TG值降低(p＜0.05)、HDL-C(p＜0.01)和PA水平有增高的趋势(p=0.075);在T2DM组呈现高的HOMA-IR值(p＜0.05);在合并EH组呈现低HOMA-IR值(p＜0.05).在汉族NGT组中呈现低的FPG和INS、HOMA-IR值(p＜0.05)、高水平的HDL-C(p＜0.01);在T2DM组呈现高WHR值(p＜0.05);在合并EH组呈现高SBP趋势(p=0.058).6.单倍型CTCAC与汉族人群罹患T2DM易感性呈负相关(p＜0.05,OR＜1);与朝鲜族人群罹患合并EH易感性呈负相关(p＜0.001,OR＜1).结论:1.KCNJ11基因位点R221C多态的A等位基因可能是延边朝鲜族和汉族T2DM保护因子,影响脂代谢水平和血清胰岛素和脂连素水平,而rs5218、rs5219、rs5215和rs1800854多态可能与延边朝鲜族和汉族T2DM易感性不相关;2.KCNJ11基因SNPs(rs5218、rs5219、rs5215、R221C、rs1800854)组成的单倍型CTCAC是延边朝鲜族T2DM合并EH及汉族T2DM保护单倍型;3.rs5219与rs5215存在完美连锁不平衡。
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