Association between Single Nucleotide Polymorphisms and Endometriosis in a Brazilian Population

Abstract

Objective To investigate the association between genetic polymorphisms in candidate genes or candidate regions and the development of endometriosis in Brazilian women.

Methods A total of 30 women between 25 and 64 years old with a diagnosis of endometriosis participated in the present study, as well as 30 matched control women from the same age group, asymptomatic and without family history of the disease. The patients genotypic and allelic frequencies of polymorphisms in the GREB1 gene (rs13394619) and in the intergenic region at position 7p15.2 (rs12700667) were analyzed and compared.

Results There was no significant difference in the frequency of genotypes for the A > G polymorphism (rs13394619) in the GREB1 gene between the two groups. However, the distribution frequencies of the genotypes for the A > G polymorphism (rs12700667) in an intergenic region on chromosome 7 were different for control patients and for patients with endometriosis, with higher frequency of the AG genotype compared to the GG between patients with the disease (odds ratio [OR] = 3.49; confidence interval [CI] = 1.47–8.26).

Conclusion The present study suggests that the polymorphism in the intergenic region of chromosome 7 is associated with the risk of developing endometriosis in a population of Brazilian women from Juiz de Fora.

Resumo

Objetivo Investigar a associação de polimorfismos genéticos em genes candidatos ou regiões candidatas com o desenvolvimento da endometriose em mulheres brasileiras.

Métodos Um total de 30 mulheres com diagnóstico de endometriose, com idade entre 25 e 64 anos, participaram da presente pesquisa, bem como 30 mulheres controle, na mesma faixa etária, assintomáticas e sem história familiar da doença. Foram analisadas e comparadas as frequências genotípicas e alélicas de polimorfismos no gene GREB1 (rs13394619) e na região intergênica na posição 7p15.2 (rs12700667) nessas pacientes.

Resultados Não houve diferença significativa na frequência dos genótipos para o polimorfismo A > G (rs13394619) no gene GREB1 entre os dois grupos. No entanto, as frequências de distribuição dos genótipos para o polimorfismo A > G (rs12700667) em uma região intergênica no cromossomo 7 foram diferentes entre as pacientes controle e com endometriose, com frequência mais alta do genótipo AG comparado ao GG entre as pacientes com a doença (odds ratio [OR] = 3,49; intervalo de confiança [IC] 95% = 1,47–8,26).

Conclusão O presente estudo sugere que o polimorfismo na região intergênica do cromossomo 7 foi associado com o risco do desenvolvimento de endometriose em uma população de mulheres de Juiz de Fora.

Keywords

endometriosis - polymorphism - single nucleotide - genetics

Palavras-Chave

endometriose - polimorfismo de nucleotídeo único - genética

Contributions

Viana P. C. S, Farah L., Tostes G., Gonçalves L. and Júnior H. G. contributed with the conception and design of the present study, data collection and analysis, interpretation of data and with the final approval of the version to be published. Mendes A. C. D. M. contributed with the writing of the article and with the final approval of the version to be published. Raposo N. R. B, Vitral G.S.F and Gerheim P.S.A.S contributed with the conception and design of the present study, data collection and analysis, and interpretation of data, the writing of the article, the critical review of the intellectual content, and with the final approval of the version to be published.

• References

• 1 Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J. Medicina interna de Harrison. 19a ed. São Paulo: Art Med; 2017
• 2 de Souza GKT, Costa JRG, de Oliveira LL, Lima LR. Endometriose x infertilidade: revisão de literatura. EEDIC 2017; 3 (01) 1-4
• 3 Treloar SA, O'Connor DT, O'Connor VM, Martin NG. Genetic influences on endometriosis in an Australian twin sample. [e-mail]. Fertil Steril 1999; 71 (04) 701-710 . Doi: 10.1016/s0015-0282(98)00540-8
• 4 Rahmioglu N, Missmer SA, Montgomery GW, Zondervan KT. Insights into assessing the genetics of endometriosis. Curr Obstet Gynecol Rep 2012; 1 (03) 124-137 . Doi: 10.1007/s13669-012-0016-5
• 5 Trovó de Marqui AB. Genetic polymorphisms and endometriosis: contribution of genes that regulate vascular function and tissue remodeling. Rev Assoc Med Bras (1992) 2012; 58 (05) 620-632 . Doi: 10.1590/S0104-42302012000500022
• 6 Uno S, Zembutsu H, Hirasawa A, Takahashi A, Kubo M, Akahane T. , et al. A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese. Nat Genet 2010; 42 (08) 707-710 . Doi: 10.1038/ng.612
• 7 Painter JN, Anderson CA, Nyholt DR. , Macgregor S, Lin J, Lee SH, et al. Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis. Nat Genet 2011; 43 (01) 51-54 . Doi: 10.1038/ng.731
• 8 Albertsen HM, Chettier R, Farrington P, Ward K. Genome-wide association study link novel loci to endometriosis. PLoS One 2013; 8 (03) e58257 . Doi: 10.1371/journal.pone.0058257
• 9 Fleiss JL, Tytun A, Ury HK. A simple approximation for calculating sample sizes for comparing independent proportions. Biometrics 1980; 36 (02) 343-346 . Doi: 10.2307/2529990
• 10 Nyholt DR, Low SK, Anderson CA, Painter JN, Uno S, Morris AP. , et al. Genome-wide association meta-analysis identifies new endometriosis risk loci. Nat Genet 2012; 44 (12) 1355-1359 . Doi: 10.1038/ng.2445
• 11 Pena SD, Di Pietro G, Fuchshuber-Moraes M. , et al. The genomic ancestry of individuals from different geographical regions of Brazil is more uniform than expected. PLoS One 2011; 6 (02) e17063 . Doi: 10.1371/journal.pone.0017063
• 12 Li Y, Hao N, Wang YX, Kang S. Association of endometriosis-associated genetic polymorphisms from genome-wide association studies with ovarian endometriosis in a Chinese population. Reprod Sci 2017; 24 (01) 109-113 . Doi: 10.1177/1933719116650753
• 13 Sundqvist J, Xu H, Vodolazkaia A. , Fassbender A, Kyama C, Bokor A, et al. Replication of endometriosis-associated single-nucleotide polymorphisms from genome-wide association studies in a Caucasian population. Hum Reprod 2013; 28 (03) 835-839 . Doi: 10.1093/humrep/des457
• 14 Osiński M, Mostowska A, Wirstlein P, Wender-Ożegowska E, Jagodziński PP, Szczepańska M. The assessment of GWAS - identified polymorphisms associated with infertility risk in Polish women with endometriosis. Ginekol Pol 2018; 89 (06) 304-310 . Doi: 10.5603/GP.a2018.0052
• 15 Sapkota Y, Fassbender A, Bowdler L, Fung JN, Peterse D. , O D, et al. Independent replication and meta-analysis for endometriosis risk loci. Twin Res Hum Genet 2015; 18 (05) 518-525 . Doi: 10.1017/thg.2015.61
• 16 Adachi S, Tajima A, Quan J, Haino K, Yoshihara K, Masuzaki H. , et al. Meta-analysis of genome-wide association scans for genetic susceptibility to endometriosis in Japanese population. J Hum Genet 2010; 55 (12) 816-821 . Doi: 10.1038/jhg.2010.118
• 17 Fung JN, Holdsworth-Carson SJ, Sapkota Y, Zhao ZZ, Jones L, Girling JE. , et al. Functional evaluation of genetic variants associated with endometriosis near GREB1. Hum Reprod 2015; 30 (05) 1263-1275 . Doi: 10.1093/humrep/dev051