细胞色素P450氧化酶基因MSP1位点多态性与早产的关联性研究

目的:探讨早产与母、婴细胞色素P450氧化酶基因(CYP1A1)MSP1位点多态性的关系.方法:于1999年到2001年,采用病例对照及核心家系的研究设计,在安徽省安庆市调查了496个核心家系,包括247个正常孕周出生的核心家系(对照核心家系)和249个早产核心家系.采用盐沉淀法提取基因组DNA,通过聚合酶链式反应(PCR)对细胞色素P450氧化酶基因MSP1位点进行基因型鉴定.采用对数-线性回归模型(log-linear model)分析母亲和婴儿CYP1A1基因MSP1位点多态性与早产的关联.观察母亲与婴儿CYPlAl基因之间的联合作用是否对早产有影响,并采用TDT方法检验早产对照核心家系CYPlAl基因MSP1位点、等位基因传递是否平衡.结果:婴儿CYPlAl基因C/C6235基因型能明显增加早产的发生危险性(RR=1.80,95%CI=1.02～3.18).同时,我们也发现母亲CYPlAl基因C/C6235基因型对早产有显著影响(RR=1.82,95%CI=1.11～2.98).母亲与婴儿CYPlAl基因之间无明显联合作用存在.对照核心家系CYPlAI基因MSP1突变等位基因传递符合孟德尔遗传规律.结论:婴儿CYPlAl基因C/C6235基因型和母亲C/C6235基因型均能够明显增加早产发生风险,在早产核心家系中CYPlAl基因MSP1突变等位基因传递不符合孟德尔遗传规律,可能是导致早产的遗传易感位点.

Association of cytochrome P450 gene MSP1 polymorphism and risk of preterm delivery

OBJECTIVE: To investigate the association of cytochrome p450 gene (CYP1A1)MSP1 polymorphisms with preterm delivery. METHODS: Between July 1999 and June 2001, we conducted a case-control study using infant-parent triads including 247 families with full-term infants and 249 families with preterm delivery infants in Anqing, China. We extracted DNA from umbilical cord blood of the infants and vein blood of their parents,and performed PCR followed by restriction enzyme MspI digestion for genotyping the CYP1A1 gene MSP1 polymorphism. We used log-linear modeling to analyze the association of CYP1A1 gene polymorphism with the risk of preterm delivery. RESULTS: CYP1A1 gene C/C6235 increased the risk of preterm delivery both in infants (RR=1.80, 95% CI=1.02-3.18) and in their mothers (RR=1.82, 95% CI=1.11-2.98) significantly.There was no interaction between mothers' and children's CYP1A1 MSP1 genotypes. The variant alleles of CYP1A1 MSP1 of control triads accorded with Mendelian transmissions. CONCLUSION: Both infant and maternal CYP1A1 C/C6235 genotype both can increase the risk of preterm delivery in our study population, which suggests a possible role of human cytochrome P450 variability in the etiology of preterm delivery.