ABCG8基因T400K多态性与胆囊结石病以及血脂水平的关系

ABCG8 T400K polymorphism in gallstone disease and its impact on the serum lipids level

目的:探讨人类ABCG8基因T400K多态性与胆囊结石病的关系,以及对血脂的影响。方法:对283例胆囊结石病人和212例健康人群采集静脉血,提取其基因组DNA,采用聚合酶链反应-限制性长度多态性分析ABCG8T400K多态性,并经DNA测序验证;测定血脂。结果:T400K在总体胆石组与对照组之间的分布无显著差异(21.6%比17.0%,P=0.205);但在男性胆石组中,K400频率明显高于对照组(25.9%比11.9%,P<0.01),女性中无差异(18.6%比21.6%,P=0.531)。胆石组血清低密度脂蛋白-胆固醇(2.64±0.88)mmol/L明显高于对照组(2.07±0.78)mmol/L,P<0.01。在TT纯合体胆石病人中,总胆固醇[(4.38±0.98)mmol/L比(4.02±0.83)mmol/L,P<0.05]和低密度脂蛋白-胆固醇[(2.69±0.87)mmol/L比(2.05±0.76)mmol/L,P<0.01]也较对照组显著增加;但在TK/KK中,胆石组和对照组的血脂无差异。结论:ABCG8基因T400K多态性影响胆固醇代谢,K400携带者是男性胆石病的危险因素。

Objective To explore the relationship between the T400K polymorphism of ABCG8 gene and gallstone disease, as well as its impact on the serum fipids level. Methods Two hundred and eighty-three patients with simple gallstone disease and 212 normal people as controls were enrolled into this study. Polymorphism of the ABCG8 gene was detected by PCR-RFLP and subsequent DNA direct sequencing. The serum lipids were measured by assay kits. Results No difference was found in the distribution of T400K between the total number of gallstone carriers and the controls （21.6% vs 17.0%, P=0.205）; nor did any difference exist between the female carriers and the controls （18.6% vs 21.6%, P=0.531）; Yet, the frequency of K400 in the male gallstone carriers and the controls was significantly higher （25.9% vs 11.9%, P〈0.01）. The levels of serum low-density lipoprotein cholesterol （LDL-C） in the patients were significantly higher than those in the controls [（2.64±0.88） mmol/L vs. （2.07±0.78） mmol/L, P〈0.01]. The patients with T400 homozygotes also exhibited higher levels of serum total cholesterol [（4.38±0.98） mmol/L vs. （4.02±0.83） mmol/L, P〈0.05] and LDL-C [（2.69± 0.87） mmol/L vs. （2.05±0.76） mmol/L, P〈0.01] than the controls, but no similar results was observed in the K400 carriers. Conclusion The T400K polymorphism of ABCG8 gene plays a genetic role in the cholesterol metabolism, and the K400 carrier is a risk factor of gallstone disease in the male.