Highlights
- •We investigated the association between six tissue inhibitor of metalloproteinase (TIMP) polymorphisms and primary ovarian insufficiency in Korean females.
- •The TIMP2G > C (rs8179090) and TIMP2G > A (rs2277698) genotypes were strongly associated with primary ovarian insufficiency.
- •Our data suggest that the TIMP2 genotypes and TIMP1 haplotypes may increase the risk of primary ovarian insufficiency in Korean women.
Abstract
Background
Until now, an association between tissue inhibitor of metalloproteinase (TIMP) polymorphisms
and primary ovarian insufficiency (POI) has not been identified. The aim of our study
was to investigate whether the TIMP polymorphisms TIMP1T > C (rs4898), TIMP1G > A (rs6609533), TIMP2G > C (rs8179090), TIMP2G > A (rs2277698), TIMP3G > A (rs135029), and TIMP4T > C (rs3755724), which regulate matrix metalloproteinases (MMPs), confer a risk
for primary ovarian insufficiency (POI) in Korean women (further studies would be
required to evaluate the associations between TIMP polymorphisms and POI in other populations).
Methods
We genotyped 137 POI patients and 236 controls for the single nucleotide polymorphism
sites using PCR–RFLP analysis. Differences in the frequencies of the TIMP1T > C (rs4898), TIMP1G > A (rs6609533), TIMP2G > C (rs8179090), TIMP2G > A (rs2277698), TIMP3G > A (rs135029), and TIMP4T > C (rs3755724) genotypes between patients and controls were compared, and odds
ratios and 95% confidence intervals were determined to measure of the strength of
the association between the genotypes and POI.
Results
The TIMP1T > C (rs4898), TIMP1G > A (rs6609533), TIMP2G > C (rs8179090), TIMP2G > A (rs2277698), TIMP3G > A (rs135029), and TIMP4T > C (rs3755724) genotypes, but especially the TIMP2 genotypes, were found more frequently in POI patients than in control subjects. Among
the four TIMP loci, the TIMP1T > C (rs4898), TIMP1G > A (rs6609533), TIMP2G > C (rs8179090), TIMP2G > A (rs2277698), TIMP3G > A (rs135029), and TIMP4T > C (rs3755724) haplotypes were identified more frequently in POI patients than
in control subjects and conferred susceptibility to POI (P <0.0001).
Conclusions
The TIMP2G > C (rs8179090) and G > A (rs2277698) alleles were strongly associated with POI.
Our data suggest that the minor TIMP2 alleles may increase POI risk in Korean women.
Keywords
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Article info
Publication history
Published online: November 27, 2018
Accepted:
November 26,
2018
Received in revised form:
November 12,
2018
Received:
July 12,
2018
Identification
Copyright
© 2018 Elsevier B.V. All rights reserved.
