Association study of five functional polymorphisms in matrix metalloproteinase-2,-3, and-9 genes with risk of primary ovarian insufficiency in Korean women

Objective: Primary ovarian insufficiency (POI) is diagnosed clinically by increased follicle-stimulating hormone (FSH) levels and estradiol (E-2) deficiency. A previous report suggests a possible association matrix metalloproteinase (MMP) and estrogen signaling pathway; however, there are no reports of MMP genetic associations with POI. Study design: Blood samples were collected from 374 karyotypically normal study participants consisting of 138 patients with POI(46, XX; mean age +/- standard deviation [SD], 31.7 +/- 3.51 years) and 236 control subjects (46, XX; 32.2 +/- 3.50 years). Five functional polymorphisms in MMP-2 (-1575G > A [rs243866] and -1306C > T 1rs2438651), MMP-3 (-1612 5A/6A [rs3025058]), and MMP-9 (-1562C > T [rs3918242] and 2678G > A [rs17576]) genes were genotyped using polymerase chain reaction-restriction fragment length polymorphism assays in a cohort of 236 controls and 138 POIs. Results: MMP-2 -1306CT + IT was associated with POI occurrence. Moreover, relatively lower serum estradiol levels were detected in healthy women with the MMP-2 -1575GA+AA/MMP-2 -1306CT+TT and MMP-2 -1306CT+TTIMMP-9 2678GG combination genotypes. Conclusions: MMP-2 -1306C > T polymorphism may contribute to an increased POI prevalence in Korean women. Further studies are needed to confirm the genetic associations in other ethnic populations. (C) 2014 Elsevier Ireland Ltd. All rights reserved.