Interaction between CYP1A1/CYP17A1 polymorphisms and parental risk factors in the risk of hypospadias in a Chinese population

Hypospadias (HS) is a common congenital malformation of the genitourinary tract in males and its etiology is viewed as multifactorial, and studies about gene-environment interaction in the etiology of HS are rare. A total of 152 cases and 151 controls were selected in the present study. Information before and during pregnancy from questionnaires finished by mothers of subjects were extracted, and the relating data were analyzed to determine the risk factors of HS. Meanwhile, maternal genomic DNA was genotyped for the single nucleotide polymorphisms (SNPs) of CYP1A1 rs1048943 and CYP17A1 rs4919686. Results of multivariable logistic regression analyses showed that several factors were associated with hypospadias risk. Analysis of the distributions of SNPs in CYP1A1 and CYP17A1 genes showed that the mutant genotype CC (OR = 4.87) of CYP1A1 rs1048943, and mutant genotype CC (OR = 5.82), recessive genotype AC + CC (OR = 2.17) and allele C (OR = 1.77) of CYP17A1 rs4919686 significantly increased the risk of HS. In addition, the additive gene-environment interactions were also found in several models. Several maternal risk factors that are associated with HS risk can interact with CYP1A1/CYP17A1 polymorphisms, which lead to infants vulnerable to occurrence of HS in Chinese populations.