Estrogen receptor-1 genetic polymorphisms for the risk of premature ovarian failure and early menopause.
BACKGROUND
The aim of this study was to investigate the role of the estrogen receptor 1 (ESR1) genetic polymorphisms for early menopause that was classified as premature ovarian failure (POF) and early menopause (EM) and to examine whether the associations of ESR1 genetic variants are different for POF and EM.


METHODS
We selected 100 POF cases and matched 100 EM cases and 200 normal menopause (NM) controls from the Korean Multi-Center Cohort. Among them, we restricted idiopathic POF and EM cases vs NM controls by excluding POF/EM cases with medical/surgical causes. The XbaI (rs9340799) and PvuII (rs2234693) in the ESR1 gene were genotyped. The single-nucleotide polymorphism (SNP) and haplotype effects were analyzed by multivariate logistic regression and haplotype analysis. Also nominal polytomous logistic regression was used to find whether ESR1 genetic variants are differently associated with POF and EM.


RESULTS
The global p values for idiopathic POF and EM were 0.08 and 0.39 (SNP-based), and <0.001 and 0.12 (haplotype-based), respectively. The XbaI genetic variant containing the X allele was marginally significantly associated with a reduced risk of idiopathic POF (OR = 0.6, 95% CI 0.3-1.0). The P-x haplotype and diplotypes significantly decreased the risk of idiopathic POF (OR = 0.5, 95% CI 0.2-0.9; OR = 0.4, 95% CI 0.2-0.9, respectively). In contrast from POF, the P-x haplotypes and diplotypes insignificantly increased the risk for both idiopathic EM (p(polytomous) = 0.009 for P-x haplotype; p(polytomous) = 0.02 for P-x diplotypes).


CONCLUSIONS
Our results suggest that the ESR1 gene including PvuII and XbaI polymorphisms may modify the risk of idiopathic premature ovarian failure (POF) but not idiopathic early menopause (EM) risk.
Yang
Jae Jeong
JJ
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
Cho
Lisa Y
LY
Lim
Yun Jeong
YJ
Ko
Kwang-Pil
KP
Lee
Kun-Sei
KS
Kim
Hyeongsu
H
Yim
Sung Vin
SV
Chang
Soung Hoon
SH
Park
Sue K
SK
D000328:Adult; D015331:Cohort Studies; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D006801:Humans; D008594:Menopause, Premature / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D011446:Prospective Studies; D056910:Republic of Korea; D012306:Risk
D047628:Estrogen Receptor alpha