Association of E-cadherin single nucleotide polymorphisms with the increased risk of endometriosis in Indian women

The objective of the present study was to investigate the association between gene E-cadherin single nucleotide polymorphisms (SNPs) and risk of developing endometriosis in Indian women and to evaluate the role of E-cadherin expression in the pathophysiology of endometriosis. A genetic association study was conducted in 715 endometriosis cases and 500 controls of Indian origin. We genotyped 160 C/A, 54 C/T and 347 G/GA SNPs of gene E-cadherin by PCR-sequencing and PCR-restriction fragment length polymorphism techniques. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D) for pair-wise linkage disequilibrium (LD) were assessed by Haploview Software. In addition, to better understand genetic contributions to the pathophysiology of endometriosis, the expression pattern of E-cadherin in the endometrium of women with and without endometriosis was analyzed by western blot and immunohistochemical analysis. The frequencies of 347GA/GA (P 0.026) and 160A/A (P 0.0019) genotypes and 347G/160A/54C (P 0.007) and 347GA/160A/54C (P 0.0001) haplotypes were significantly different between patients and controls. Strong LD was observed between 347G/GA and 160C/A loci (D 0.64) when compared with 347G/GA and 54C/T (D 0.585) or 160C/A and 54C/T (D 0.05) loci in cases. Furthermore, increased membranous E-cadherin expression was observed in cases than in controls. The expression seems to be genotype dependent. In conclusion, the E-cadherin 347GA/GA and 160A/A genotypes and 347GA/160A/54C and 347G/160A/54C haplotypes may jointly modify the risk of endometriosis in Indian women. In addition, the differential expression of E-cadherin may play an important role in pathogenesis of endometriosis.