FXR基因多态性与脓毒症的相关性研究

Clinical Correlations between the Polymorphisms of FXR Gene and Sepsis

目的探讨华北汉族人群法尼酯衍生物X受体(farnesoid X receptor,FXR)基因多态性与脓毒症易感性和临床转归的相关性。方法本研究采用病例-对照研究方法,使用改良的多重连接酶检测反应技术(iMLDR)对FXR基因中11个常见的单核苷酸多态性(SNP)位点进行基因分型,探讨华北汉族人群法尼酯衍生物X受体(FXR)基因多态性与脓毒症易感性和临床转归的相关性。结果rs1030454 AG/AG+GG基因型发生脓毒症的风险较AA型低,比值比和95%置信区间[OR(95%CI)]分别为0.66(0.45~0.97),P=0.036和0.69(0.47~0.99),P=0.046。脓毒症患者中rs56163822 TT较GG/GG+GT、rs7960501 CC较TT/TT+CT、rs17030270 GG较AA+AG、rs1111041 CC较TT+TC、rs17030295 TT较CC/CC+CT、T等位基因型较C、rs35735 TT较GG/GG+GT发生重度器官功能障碍的风险高。rs1030454 AG+GG较AA、G等位基因型较A发生重度器官功能障碍的风险低。rs35735 GT/GT+TT较GG、T等位基因型较G死亡风险增高。没有发现基因多态性与脓毒性休克相关。结论在华北汉族人群中,FXR遗传多态性可能参与了脓毒症的发生和预后。

Objective To investigate the clinical relevance of farnesoid X receptor(FXR)gene polymorphisms with sepsis in Han population of North China.Methods Eleven common single nucleotide polymorphisms(SNPs)in the FXR gene were genotyped in 303 septic patients and 303 controls using an improved multiplex ligation detection reaction(iMLDR)technique.Unconditional logistic regression analysis was used to evaluate the correlation between genotype with susceptibility to sepsis and clinical outcome(septic shock/organ dysfunction/death).Results The risk of sepsis in rs1030454 AG/AG+GG genotype was lower than that in AA genotype,and the odds ratio(OR)and 95%confidence interval(CI)were 0.66(0.45-0.97),P=0.036;0.69(0.47-0.99),P=0.046.rs56163822TT compared with GG/GG+GT,rs7960501 CC compared with TT/TT+CT,rs17030270 GG compared with AA+AG,rs1111041 CC compared with TT+TC,rs17030295 TT compared with CC/CC+CT,T allele compared with C allele,rs35735 TT compared with GG/GG+GT,the former had a higher risk of serious organ dysfunction.Compared with AA and A allele,rs1030454 AG+GG and G allele had a lower risk of severe organ dysfunction.rs35735 GT/GT+TT compared with GG,T allele compared with G,increased the risk of death.No association was founded in gene polymorphisms and septic shock.Conclusion FXR genetic polymorphism may be involved in the occurrence and development of sepsis in the Han population of North China.