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

•The purpose of this study was to investigate associations between MMP genes and POI.•Five functional polymorphisms in MMP-2, MMP-3, and MMP-9 genes were analyzed.•MMP-2 -1306CT + TT affected POI prevalence and estradiol levels of healthy women.•MMP-2 -1306C > T may contribute to an increased POI prevalence in Korean women.

ObjectivePrimary ovarian insufficiency (POI) is diagnosed clinically by increased follicle-stimulating hormone (FSH) levels and estradiol (E2) 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 designBlood 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 [rs243865]), 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.ResultsMMP-2 -1306CT + TT 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 + TT/MMP-9 2678GG combination genotypes.ConclusionsMMP-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.