Gene Environment Interactions Between the COL9A1 Gene and Maternal Drinking of Alcohol Contribute to the Risk of Congenital Talipes Equinovarus

Background: Previous studies have indicated that both genetic and environmental factors contribute to the risk of congenital talipes equinovarus (CTEV). The COL9A1 gene encodes one of the three alpha chains of type IX collagen, which is a key collagen component of hyaline cartilage. Our study aimed to evaluate the effect of COL9A1 gene polymorphisms on susceptibility to CTEV in the Han Chinese population. Methods: A total of 2205 unrelated subjects comprising 692 CTEV patients and 1513 healthy controls were recruited. Demographic and characteristic information was collected, including maternal smoking and maternal drinking. Genetic association analyses and gene-environment interaction analyses were conducted based on the genotypic data of 36 tag single nucleotide polymorphisms (SNPs). Results: Although there was no association between genotyped SNPs and CTEV, a gene-environment interaction signal between SNP rs6455357 and maternal drinking was identified. Furthermore, significant heterogeneity was identified for this interaction signal when stratified by maternal drinking. For subjects with never maternal drinking, the A allele of SNP rs6455357 was significantly associated with a decreased risk of CTEV. In contrast, the A allele was associated with an increased risk of CTEV in the "occasional" and "often" groups. Conclusions: Our results indicate a combined effect of genetics and environmental factors on the etiology of CTEV. This study increases our understanding of the etiology of CETV and provides useful information for genetic counseling for at-risk families for the development of prevention programs and improved management.