Abstract
Research question
Are the candidate genes for age at menarche associated with a risk of endometriosis?
Design
Fifty-two candidate single nucleotide polymorphisms (SNP) for age at menarche, their
gene–gene and gene–environment interactions were analysed for possible association
with endometriosis in a sample of 395 patients and 981 controls. Association of the
polymorphisms was analysed using logistic regression according to three main genetic
models (additive, recessive and dominant). The gene–gene and gene–environment interactions
were analysed for the second-, third- and fourth-order models with adjustment for
covariates and multiple comparisons with subsequent cross-validation.
Results
Sixteen SNP for age at menarche out of the 52 studied were associated with endometriosis.
Polymorphism rs6589964 BSX was associated with endometriosis according to the additive and recessive models
(OR 1.27–1.47, Pperm ≤ 0.006). Fourteen SNP were associated with the disease within 12 most significant
models of gene–gene interactions (Pperm ≤ 0.008). Twelve SNP involved in 10 most significant models of SNP–induced abortion
interactions are associated with endometriosis. Fourteen of the 16 polymorphisms associated
with endometriosis demonstrated pleiotropic effects: they were also associated with
either age at menarche (7 SNP) or height and/or body mass index (10 SNP) in the studied
sample. The 16 SNP associated with endometriosis and 316 SNP linked to them have regulatory
and expression quantitative trait locus significance for 28 genes contributing to
the G alpha signal pathway (fold enrichment 31.09, PFDR = 0.001) and responses to endogenous stimuli (fold enrichment 16.01, PFDR = 0.027).
Conclusions
Sixteen SNP for age at menarche out of the 52 studied were associated with endometriosis.
Keywords
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Biography
Professor Mikhail Churnosov is Head of the Department of Biomedical Disciplines of the Belgorod State University. His areas of research activity include the study of the role of polymorphisms of candidate genes, gene–gene and gene–environmental interactions in the formation of frequently occurring multifactorial diseases among the Russian population.
Article info
Publication history
Published online: May 14, 2020
Accepted:
April 21,
2020
Received in revised form:
February 25,
2020
Received:
November 19,
2019
Declaration: The authors report no financial or commercial conflicts of interest.Identification
Copyright
© 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
