The Polymorphic Locus rs780093 of the GCKR Gene Is Associated with the Risk of Infertility in Endometriosis

T. A. Ponomareva, O. B. Altukhova, Irina Ponomarenko, Mikhail Churnosov
In: Russian Journal of Genetics · 2025 · vol. 61(8) , pp. 987–996 · doi:10.1134/s1022795425700516 · W4413812022
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Abstract

In this study, we examine the associations of nine polymorphic loci associated with the level of sex hormone binding globulin (SHBG) with the development of infertility in women with genital endometriosis. The study was conducted on a sample of 395 patients with genital endometriosis (132 women with genital endometriosis and concomitant infertility, 263 women with genital endometriosis without infertility), natives of the Central Black Earth Region of Russia. Genotyping of nine polymorphic loci associated with SHBG levels according to previously conducted genome-wide association studies (GWAS) was performed: rs12150660 SHBG, rs10454142 PPP1R21, rs780093 GCKR, rs17496332 PRMT6, rs3779195 BAIAP2L1, rs440837 ZBTB10, rs7910927 JMJD1C, rs4149056 SLCO1B1, rs8023580 NR2F2. It was found that the genotype TT rs780093 GCKR is associated with a low risk of infertility in endometriosis (OR = 0.43; p = 0.017; pperm = 0.019). It has been identified that interlocus interactions rs8023580 NR2F2–rs10454142 PPP1R21–rs17496332 PRMT6 are significantly associated with the risk of infertility in genital endometriosis (Wald criterion WH = 19.15, pperm ≤ 0.001). Combinations of genotypes rs8023580-TT NR2F2–rs10454142-TT PPP1R21–rs17496332-AA PRMT6 (beta = 0.71, p = 0.042), rs8023580-TC NR2F2–rs10454142-CC PPP1R21–rs17496332-AA PRMT6 (beta = 1.55, p = 0.025), and rs8023580-TC NR2F2–rs10454142-TT PPP1R21–rs17496332-AG PRMT6 (beta = 1.92, p = 0.027) are risk factors for infertility in genital endometriosis. Thus, the polymorphic locus rs780093 GCKR and the interlocus interactions rs8023580 NR2F2–rs10454142 PPP1R21–rs17496332 PRMT6 are associated with the risk of infertility in endometriosis.

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endometriosisinfertility

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