肺表面活性蛋白A基因多态性与呼吸道合胞病毒下呼吸道感染的相关性研究

Association of surfactant protein a gene polymorphisms with respiratory syncytial virus lower respiratory tract infection

目的探讨肺表面活性蛋白(SP)-A1-1101C/T和SP-A2-1649G/C位点基因多态性与呼吸道合胞病毒下呼吸道感染(RSV-LRTI)的相关性。方法应用聚合酶链反应-限制性酶切片段长度多态性(PCR-RFLP)分析法检测200例病例组和150例健康对照组2个位点的基因多态性,并进行基因型、等位基因型频率分析;采用DNA测序法进行测序分析。结果 1.病例组SP-A1-1101C/T位点TT、CT基因型频率分别为76.0%、24.0%,T、C等位基因频率分别为88.0%、12.0%;对照组TT、CT基因型频率分别为80.7%、19.3%,T、C等位基因频率分别为90.3%、9.7%,两组基因型及等位基因频率差异无统计学意义(χ2=1.088、0.953,P>0.05)。2.病例组SP-A2-1649G/C位点CC、CG、GG基因型频率分别为41.5%、50.5%、8.0%,C、G等位基因频率分别为66.8%、33.2%;对照组CC、CG、GG基因型频率分别为43.3%、49.3%、7.4%,C、G等位基因频率分别为68.0%、32.0%,两组基因型及等位基因频率无统计学意义(χ2=0.141、0.122,P>0.05);但该位点基因型和等位基因在轻度和重度患儿间的差异有统计学意义(χ2=6.664、5.207,P<0.05),携带G等位基因的个体患重度RSV-LRTI的风险是患轻度风险的1.656倍,(OR=1.656,95%CI:1.072～2.559,P=0.023<0.05)。结论温州地区汉族儿童存在SP-A1-1101C/T、SP-A2-1649G/C基因多态性,未发现其与RSV-LRTI疾病易感性存在关联,但携带SP-A2-1649G等位基因的个体患重度RSV-LRTI的风险是患轻度风险的1.656倍,表明G等位基因可能是影响RSV-LRTI疾病严重程度的一个候选基因。

Objective： To explore the association of the single nucleotide polymorphism（SNP） of surfactant protein（SP）-A1-1101C/T and SP-A2-1649G/C gene with disease susceptibility and severity in children with respiratory syncytial virus lower respiratory tract infection（RSV-LRTI）.Methods： Polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） was used to identify the polymorphisms at two positions above in two hundreds children（case group） and 150 healthy children（control group）,and the genotype frequencies and allele frequencies were analyzed simultaneously;Some PCR fragments were selected from the case group and the control group randomly,and sequence analysis was used for detecting the gene polymorphisms.Results： 1.The genotype frequency of SP-A1-1101C/T was 76.0%（TT）,24.0%（CT）,The frequency of each allele was 88.0%（T）,12.0%（C） in the case group and 80.7%（TT）,19.3%（CT）,90.3%（T）,9.7%（C） in the control group.CC genotype wasn′t found.There was no significant difference in genotype and allele frequency between two groups（χ2=1.088,0.953,P0.05）.2.The genotype frequency of SP-A2-1649G/C was 41.5%（CC）,50.5%（CG）,8.0%（GG） respectively in case group,and 43.3%（CC）,49.3%（CG）,7.4%（GG） respectively in control group,The frequency of each allele was 66.8%（C）,33.2%（G） respectively in case group,and 68.0%（C）,32.0%（G） in control one,There was no significant difference in genotype and allele frequency between two groups（χ2=0.141,0.122,P0.05）;but there was significant difference between the mild and severe group for the genotype and allele frequency（χ2=6.664,5.207,P0.05）,the frequency of SP-A2-1649G allele was significantly increased in severe group（OR=1.656,95%CI：1.072～2.559,P=0.0230.05）.Conclusions： SP-A1-1101C/T and SP-A2-1649G/C gene polymorphisms are both present in Han children in Wenzhou area,and that do not correlated with RSV-LRTI susceptibility,but the frequency of SP-A2-1649G allele was significantly increased in severe group,and the odds ratio was 1.656,It suggested that G allele of SP-A2-1649 might be an candidate gene for the severity of RSV-LRTI.