基因多态性与急性一氧化碳中毒后迟发性脑病的关联研究

The association study of WWP2 gene polymorphisms with delayed encephalopathy after acute carbon monoxide poisoning

目的探讨含WW结构域的E3泛素蛋白连接酶2(WWP2)基因的2个单核苷酸多态性位点(rs3790088、rs4247109)与急性一氧化碳中毒后迟发性脑病(DEACMP)潜在的关联性,探寻引起DEACMP的遗传易感基因。方法选择2006年11月至2017年12月就诊的急性一氧化碳中毒(ACMP)昏迷抢救成功患者,共235例DEACMP患者和429例ACMP患者,ACMP患者均随访90 d以上且未发生DEACMP。采用血液基因组DNA提取试剂盒进行外周血DNA提取;运用Sequenom分型检测技术分析WWP2基因多态性与DEACMP的遗传易感性。DEACMP患者入院后每3 d评估一次《长谷川痴呆量表》(HDS)和《日常生活能力量表》(ADL),评估患者智力和生活能力受损程度。基因型分布是否符合Hardy-Weinderg平衡定律用拟合优度χ^2检验,两组患者基因关联性分析采用2×2四格表或2×3列联表χ^2检验,共显性遗传模式用2×3列联表χ^2检验。结果rs3790088位点包含226例DEACMP患者和414例ACMP患者,rs4247109位点包含234例DEACMP患者和428例ACMP患者。DEACMP和ACMP患者各基因型Hardy-Weinberg平衡检验差异无统计学意义(P>0.05)。DEACMP与ACMP患者rs3790088和rs4247109位点基因型及等位基因频率分布差异均无统计学意义(P>0.05)。按性别分组后,DEACMP与ACMP患者rs3790088和rs4247109位点基因型及等位基因频率分布差异均无统计学意义(P>0.05)。三种遗传模式(共显性遗传、显性遗传、隐性遗传)下rs3790088和rs4247109位点基因型与DEACMP发病无关联(P>0.05)。结论WWP2基因的2个单核苷酸多态性位点(rs3790088、rs4247109)和DEACMP的发病尚无法确定存在遗传相关性。

Objective To investigate the association of WWP2 single nucleotide polymorphism(rs3790088,rs4247109)with delayed encephalopathy after acute carbon monoxide poisoning(DEACMP),and explore the influences of DEACMP genetic predisposition.Methods From November 2006 to December 2017,235 DEACMP cases and 429 acute carbon monoxide poisoning(ACMP)cases were selected.All ACMP patients were followed up for more than 90 days without DEACMP.The DNA in all blood samples were extracted with the blood Genome DNA Extraction Kit.The method of Sequenom Mass Array SNP technique was used to detect the genotype and allele of WWP2.All DEACMP patients were assessed every 3 days after hospitalization by the Hasegawa Dementia Scale(HDS)and Activity of Daily Living Scale(ADL).The distribution of genotypes in conformty with Hardy-Weinderg law was analyzed by goodness-of-fitχ^2 test,andχ^2 test was used for association analysis.Results For rs3790088,there were 226 DEACMP cases and 414 ACMP cases.For rs4247109,there were 234 DEACMP cases and 428 ACMP cases.For rs3790088 and rs4247109 in WWP2 gene:there were not significant differences in the gene genotype distribution and allele frequency of both DEACMP group and ACMP group(P>0.05).According to gender,there were not significant differences in WWP2 gene genotype distribution and allele frequency between two female groups and two male groups(P>0.05).After analysis by genetic model,the genotype distributions in both DEACMP group and ACMP group were not significantly differences in three genetic models(codominant genetic model,recessive genetic model and dominant genetic model,P>0.05).Conclusion It has not confirmed the genetic correlation between the two gene single nucleotide polymorphisms(rs3790088,rs4247109)of WWP2 gene and the incidence of DEACMP.