谷胱甘肽硫转移酶T1基因多态性与尿道下裂的相关研究

Correlative analysis of between glutathione S-transferase gene polymorphisms and hypospadias

目的 探讨谷胱甘肽硫转移酶（GST） T1基因多态性与尿道下裂遗传易感性的关系.方法 采用病例对照方法,选择尿道下裂患儿和正常健康男性各116例,对尿道下裂患儿采用Duckett法进行分型,采用Donnahoo法评估阴茎弯曲程度.对所有研究对象详细了解胎儿出生时情况及其母亲妊娠期被动吸烟、农药/化工试剂毒物接触暴露情况;采集外周静脉血,分离血清和血细胞;采用酶联免疫吸附试验（ELISA）法检测血清GST活力;提取细胞DNA,采用聚合酶链反应（PCR）检测GSTT1基因型,并分析各基因型与尿道下裂遗传易感性的关系.结果 尿道下裂组出生低体重儿的发生率（7.8％）较对照组（1.7％）升高（x2 =4.676,P＜0.05）;尿道下裂组早产儿的发生率（4.2％）与对照组（3.4％）比较差异无统计学意义（x2 =0.115,P＞0.05）.尿道下裂组患儿母亲妊娠期被动吸烟率（23.3％）高于对照组（10.3％,x2=6.330,P＜0.05）;尿道下裂组患儿母亲妊娠期对农药或化工类毒物接触率（31.9％）高于对照组（12.9％,x2=11.997,P＜0.01）.血清GST酶活力尿道下裂组[（3.89±1.13） ng/ml]低于对照组[（4.232±1.370） ng/ml,t=2.088,P＜0.05].尿道下裂组GSTT1（-）基因型分布（59.5％）高于正常对照组（45.7％）,差异有统计学意义（x2 =4.277,P＜0.05）,GSTT1（-）基因型增加了患尿道下裂的风险性[比值比（OR）=1.712,P＜0.05].结论 出生低体重、母亲妊娠期被动吸烟和对农药、化工类毒物的环境暴露可能是尿道下裂的易感因素;GSTT1基因多态性与尿道下裂的发生可能有密切关系;GSTT1基因可能是尿道下裂发生的候选基因.

Objective To investigate the association of hypospadias and glutathione S-transferases （GST） T1 gene polymorphism.Methods Blood samples were collected of 116 patients with hypospadias （the case group） and 116 normal healthy men （the control group）.GSTT1 genetype was identified by polymerase chain reaction （PCR）.The GST activity was detected with enzyme linked immunosorbent assay （ELISA）.Analysis of the patients＇ birth situation and their mothers＇ epidemiological situation during pregnancy.Results The incidence of low birth weight of the hypospadias group 7.8% were high than that of the control group 1.7% （x2 =4.676,P 〈 0.05）.Passive smoking and pesticide/chemical exposure during pregnancy increased the risks of hypospadias in birth rate （x2 =4.676,P 〈 0.05;x2 =6.330,P 〈 0.05;x2 =11.997,P 〈0.01）.The GST activity of the hypospadias group [（3.89 ± 1.13） ng/ml] was lower than that of the control group [（4.232 ± 1.370） ng/ml,t =2.088,P 〈0.05].The rat of GSTT1 （-）genotype of the hypospadias group 59.5% was higher than that of the control group （45.7%,x2 =4.277,P 〈0.05）.Genotype GSTT1 （-） increases the risk of hypospadias risk [odds ratio （OR） =1.7t2,P 〈0.05].Conclusion Low birth weight,passive smoking and pesticide/chemical exposure during pregnancy may be the risk factors for hypospadias.There may be closely relationship between GSTT1 （-） gene polymorphisms and the incidence of hypospadias.GSTT1 may be the andidate gene of hypospadias.