中国人群HLA-Cw、KIR2D受体基因多态性分析

摘要

目的 分析中国南、北方两个汉族人群、一个蒙古族人群的人类白细胞抗原-Cw(human leucocyte antigen-Cw,HLA-Cw)遗传多态性;进一步分析南、北方汉族人群杀伤细胞免疫球蛋白样受体2D(killer immunloglobulin-like receptor 2D,KIR2D)基因的遗传多态性、与HLA-Cw的组合特点.方法 采用聚合酶链反应-序列特异性引物技术(polymerase chain reaction-sequence specific primer,PCR-SSP)检测湖南地区112名汉族人群、内蒙古地区98名汉族人群、内蒙古地区83名蒙古族人群HLA-Cw基因、第80位密码子(Lys80、Ash80)多态性;检测两个汉族人群KIR2DL 1/2/3、KIR2DS 1/2基因分布.结果 (1)湖南地区汉族人群与内蒙古地区汉族、蒙占族人群在HLA-Cw等位基因、第80位密码子的频率差异均有非常显著的统计学意义(P＜0.001),而内蒙古地区汉族、蒙古族人群之间上述频率差异无统计学意义(P＞0.05).(2)南、北方两个汉族人群间,5个KIR2D基因频率、各基因型频率差异无统计学意义(P＞0.05).(3)两个汉族人群均以Asn80/Asn80,2DL1+/2DL2-/2DL3+/2DS1-/2DS2-组合模式最为常见(45/112、29/98);其次为Asn80/Asn80,2DL1+/2DL2-/2DL3+/2DS1+/2DS2-(18/112,16/98)和Asn80/Lys80,2DL1+/2DL2-/2DL3+/2DS1-/2DS2-(11/112,17/98).Lys80/Lys80,2DL1+/2DL2-/2DL3+/2DS1-/2DS2-组合模式的频率差异有统计学意义(1/112,8/98;Fisher's P=0.0134),其余11种组合模式在两个人群间的频率差异均无统计学意义(P＞0.05).结论 提供了中国南方湖南地区、北方内蒙古地区正常汉族人群的HLA-Cw、5个KIR2D受体基因多态性数据、蒙古族人群HLA-Cw DNA分型数据;提示我国南、北方汉族人群在HLA-Cw第80位密码子、KIR2D受体基因的组合层面上可能存在着以抑制性信号通路为优势的共同特点.%Objective To explore the genetic variations of HIA-Cw and 5 KIR2D loci in 2 Chinese Han populations residing at Southem and Noahem mainland China,respectively,and to investigate the HLA-Cw polymorphism of a Mongolian ChinesC population.Methods HLA-Cw genotyping was performed in a total of 293 healthy individuals including 1 Southem Han population living in Hunan Province(n=1 12), 1 Northern Han population(n=98) and 1 Mongolian Chinese population(n=83)in the Inner Mongolia Autonomous Region,using polymerase chain reaction-secluence specific primer(PCR-SSP)technique.Dimorphism at residue 80 of domain in the HLA-Cw molecule was exalnined by an additional set of PCR-SSP reactions.PCR-SSP was also used to detect the presence or absence of inhibitory KIR2DL1/2DL2/2DL3 loci and activating KIR2DS1/2DS2 loci for the 2 Han populations.Results The main findings were:(1) Very significant frequency difference in the HLA-Cw alldes and dimorphism at codon 80 was detected between Human Han and Northern Han population.and between Hunan Han and Mongolian population(P<0.001),while there Was n0 such difference between the 2 Northem Chinese populations(P>0.05);(2)7Lhere was no significant difference in frequencies of either the 5 individual KIR2D genes or the genotype distributions between the 2 Han populations(P>0.05);(3)Asn80/Asnn80,2DLl+/2DL2-/2DL3+/2DSl-/2DS2- predominated in both Han populations(45/112,29/ 98).followed by Asns80/Asn80,2DLl+/2Du-/2DL3+/2DS1+/2DS2-(18/112,16/98)and Asn80/Lys80,2DLl+/ 2DL2-/2DL3+/2DSl-/2DS2-(11/112,17/98).Among the 12 types of HLA-Cw codon 80 and KIR2D combinations,onlv LvS80/Lvsm,2DLI+/2DL2-/2DL3+/2DS1-/2DS2- showed marginally significant frequency difference between the 2 Hail populatious(1/1 12 vs 8/98;Fisher's P=0.0134).Conclusion Our study provided the polymorphism data of HLA-(Cw gene for 3 Chinese populations with different geographic and/or ethnic background, we further analyzed the distribufion of 5 KIR2D receptor genes in 2 Hart populations.Our data suggest that in spite of HLA-Cw heterogeneity,remmkable similarities may exist between the Southern and Northern Chinese Han populations at the combinational level 0f HLA-Cw and KIR2D,which are characterized by preponderant inhibitory signal pathways.