A microRNA-520 mirSNP at the MMP2 gene influences susceptibility to endometriosis in Chinese women

The MMP2 gene has been implicated in the pathogenesis of endometriosis. We investigated the role and function of single-nucleotide polymorphisms (SNP) of MMP2 in relation to endometriosis. First a case-control study was conducted and 17 SNPs were examined in 211 patients and 344 controls. Regression analysis was used to evaluate the genetic effect. We used reporter assay to validate the functional consequences of the significant SNP. Two SNPs (rs243832 and rs7201) had P-values <0.05 and they are in strong linkage disequilibrium (D' = 0.96 and r(2) = 0.47). Further analysis showed that rs7201 but not rs246832 was an independent risk factor and the risk C allele of rs7201 had an odds ratio (OR) of 1.88 (P = 0.004). SNP rs7201 is located at the 3'-untranslated region and is predicted to be within the microRNA-520g binding site. The reporter assay for rs7201 showed that the risk C allele had a higher expression level than the A allele (P = 0.027). Using microRNA-520g mimic and inhibitor, the results indicated that the A allele but not the risk C allele can be regulated by microRNA-520g. The C allele of SNP rs7201 increases a risk for endometriosis because of out of regulation by microRNA-520g. Journal of Human Genetics (2013) 58, 202-209; doi: 10.1038/jhg.2013.1; published online 31 January 2013