Molecular-genetic analysis of polymorphic loci c.454-397T/C and c.454-351A/G of the estrogen receptor gene ESR1 in couples with idiopathic infertility

  • M. Y. Tyrkus Institute of Hereditary Pathology, NAMS of Ukraine, Ukraine, 79000, Lviv, Lysenko str., 31-a

Abstract

Aim. To establish the association of polymorphic locus 397 T>C and 351 A>G of the gene ESR1 with unsuccessful attempts of extracorporeal fertilization in couples. Methods. DNA from peripheral blood leukocytes was isolated and purified using a modified salting out method. Extracted DNA was amplified by polymerase chain reaction (PCR). To identify the mutations of the estrogen receptor gene the PCR products were subsequently digested with the restriction enzymes. The PCR products were fractionated by electrophoresis in 2 % agarose gel. Results. A molecular-genetic study of polymorphic variants of ESR1 gene c.454–397 T> C (PvuII) and c.454–351 T> C (XbaI) was carried out in 23 couples with idiopathic infertility and failed extracorporeal fertilization and 15 couples without a history of reproductive disorders and cases of extracorporeal fertilization, who have two or more children (as control group). The distribution of genotypes and polymorphic variants of the gene ESR1 among the subjects was determined and statistical analysis was performed. It was found a slightly higher frequency of genotype ESR1 453–397TT (pp) among the couples with unsuccessful attempts of extracorporeal fertilization (32.6 %) compared to the control group pairs (23.3 %), which increases the risk of unsuccessful extracorporeal fertilization by 1.59 times, The genotype c.454–351 AA (xx) was also more frequent among the couples with unsuccessful extracorporeal fertilization (39.1 %) compared to the control group pairs (23.3 %), which increases the risk of unsuccessful extracorporeal fertilization by 2.11 times. Statistically significant differences (χ2 = 3,72, r≤0,05) were found between the two groups of subjects by the frequency of alleles of G (X) and A (x) of the locus c.453–351 A> G of ESR1 gene. Calculation of the odds ratio revealed the association of allele A(x) with probable increase in unsuccessful attempts of extracorporeal fertilization by 1.91 times with confidence interval 0.99–3.7. Conclusions. One of the genetic factors associated with the increased risk of unsuccessful extracorporeal fertilization is the presence of allele A(x) of polymorphic locus c.453–351 A> G of ESR1 gene.

Keywords: gene ESR1, extracorporeal fertilization, estrogen receptor, idiopathic infertility, molecular-genetic study.

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