Gene Polymorphisms in FAS (Rs3740286 and Rs4064) Are Involved in Endometriosis Development in Brazilian Women, but not those in CASP8 (rs13416436 and rs2037815)

Cristina Wide Pissetti; Sarah Cristina Sato Vaz Tanaka; Andrezza Cristina Cancian Hortolani; Alessandra Bernadete Trovó de Marqui

doi:10.1055/s-0038-1667183

Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics, Inhaltsverzeichnis

CC BY 4.0 · Rev Bras Ginecol Obstet 2018; 40(08): 450-457
DOI: 10.1055/s-0038-1667183

Original Article

Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil

Gene Polymorphisms in FAS (Rs3740286 and Rs4064) Are Involved in Endometriosis Development in Brazilian Women, but not those in CASP8 (rs13416436 and rs2037815)

Polimorfismos do gene FAS (rs3740286 e rs4064) estão envolvidos no desenvolvimento de endometriose em mulheres brasileiras, mas não os no CASP8 (rs13416436 e rs2037815)

Cristina Wide Pissetti

¹Department of Obstetrics and Ginecology, Universidade Federal da Paraíba, João Pessoa, PB, Brazil

,

Sarah Cristina Sato Vaz Tanaka

²Department of Patology, Genetics and Evolution, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil

,

Andrezza Cristina Cancian Hortolani

²Department of Patology, Genetics and Evolution, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil

,

Alessandra Bernadete Trovó de Marqui

²Department of Patology, Genetics and Evolution, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil

› Institutsangaben

Abstract

Objective The present study aims to investigate the association between caspase-8 (CASP8) (rs13416436 and rs2037815) and Fas cell surface death receptor (FAS) (rs3740286 and rs4064) polymorphisms with endometriosis in Brazilian women.

Methods In the present case-control study, 45 women with a diagnosis of endometriosis and 78 normal healthy women as a control group were included. The genotyping was determined by real-time polymerase chain reaction (PCR) with Taqman hydrolysis probes (Thermo Fisher Scientific, Darmstadt, Germany). Genotypic and allelic frequencies were analyzed using Chi-squared (χ²) test. In order to determine the inheritance models and haplotypes ,SNPStats (Institut Català d'Oncologia, Barcelona, Spain) was used. Levels of 5% (p = 0.05) were considered statistically significant.

Results No significant difference was observed in genotypic or allelic frequencies between control and endometriosis groups for rs13416436 and rs2037815 (CASP8 gene). On the other hand, a significant difference between rs3740286 and rs4064 (FAS gene) was found. Regarding polymorphisms in the FAS gene, a statistically significant difference was found in co-dominant and dominant models. Only the haplotype containing the rs3740286A and rs4064G alleles in the FAS gene were statistically significant.

Conclusion The polymorphisms in the CASP8 gene were not associated with endometriosis. The results indicate an association between FAS gene polymorphisms and the risk of developing endometriosis.

Resumo

Objetivo Investigar a associação entre os polimorfismos dos genes caspase-8 (CASP8) (rs13416436 e rs2037815) e FAS (rs3740286 e rs4064) em mulheres brasileiras com endometriose.

Métodos Trata-se de um estudo do tipo caso-controle, no qual foram incluídas 45 mulheres com diagnóstico de endometriose e 78 controles. A genotipagem das amostras foi determinada usando a reação em cadeia de polimerase em tempo real com sondas de hidrólise TaqMan (Thermo Fisher Scientific, Darmstadt, Germany). As frequências genotípicas e alélicas foram analisadas usando o teste do qui-quadrado. O SNPStats (Institut Català d'Oncologia, Barcelona, Espanha) foi usado para determinar os modelos de herança e os haplótipos. Os níveis de significância estatística considerados foram de 5% (p = 0,05).

Resultados Não foi observada diferença significativa nas frequências genotípicas ou alélicas entre os grupos de controle e de endometriose para os polimorfismos rs13416436 e rs2037815 (gene CASP8). Por outro lado, foi encontrada uma diferença significativa entre os polimorfismos rs3740286 e rs4064 (gene FAS). Em relação aos polimorfismos do gene FAS, foi encontrada uma diferença estatisticamente significativa nos modelos codominante e dominante. Apenas o haplótipo contendo os alelos rs3740286A e rs4064G no gene FAS foi estatisticamente significativo.

Conclusão Não há associação entre os polimorfismos do gene CASP8 e endometriose. Entretanto, há associação entre os polimorfismos do gene FAS e o risco de desenvolver endometriose.

Keywords

endometriosis - apoptosis - genetic polymorphism - real-time polymerase chain reaction - genetic predisposition to disease

Palavras-chave

endometriose - apoptose - polimorfismo genético - reação em cadeia da polimerase em tempo real - predisposição genética para doença

Volltext

Referenzen

References
1 Bulun SE. Endometriosis. N Engl J Med 2009; 360 (03) 268-279 . Doi: 10.1056/NEJMra0804690
2 Giudice LC. Clinical practice. Endometriosis. N Engl J Med 2010; 362 (25) 2389-2398 . Doi: 10.1056/NEJMcp1000274
3 Fourquet J, Gao X, Zavala D. , et al. Patients' report on how endometriosis affects health, work, and daily life. Fertil Steril 2010; 93 (07) 2424-2428 . Doi: 10.1016/j.fertnstert.2009.09.017
4 Pluchino N, Wenger JM, Petignat P. , et al. Sexual function in endometriosis patients and their partners: effect of the disease and consequences of treatment. Hum Reprod Update 2016; 22 (06) 762-774 . Doi: 10.1093/humupd/dmw031
5 Soliman AM, Yang H, Du EX, Kelley C, Winkel C. The direct and indirect costs associated with endometriosis: a systematic literature review. Hum Reprod 2016; 31 (04) 712-722 . Doi: 10.1093/humrep/dev335
6 Berker B, Seval M. Problems with the diagnosis of endometriosis. Womens Health (Lond) 2015; 11 (05) 597-601 . Doi: 10.2217/whe.15.44
7 Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril 1997; 67 (05) 817-821 . Doi: 10.1016/S0015-0282(97)81391-X
8 Agic A, Djalali S, Diedrich K, Hornung D. Apoptosis in endometriosis. Gynecol Obstet Invest 2009; 68 (04) 217-223 . Doi: 10.1159/000235871
9 Taniguchi F, Kaponis A, Izawa M. , et al. Apoptosis and endometriosis. Front Biosci (Elite Ed) 2011; 3: 648-662 . Doi: 10.2741/277
10 Harada T, Taniguchi F, Izawa M. , et al. Apoptosis and endometriosis. Front Biosci 2007; 12: 3140-3151 . Doi: 10.2741/2302
11 Nasu K, Nishida M, Kawano Y. , et al. Aberrant expression of apoptosis-related molecules in endometriosis: a possible mechanism underlying the pathogenesis of endometriosis. Reprod Sci 2011; 18 (03) 206-218 . Doi: 10.1177/1933719110392059
12 Tummers B, Green DR. Caspase-8: regulating life and death. Immunol Rev 2017; 277 (01) 76-89 . Doi: 10.1111/imr.12541
13 Xu Y, He B, Li R. , et al. Association of the polymorphisms in the Fas/FasL promoter regions with cancer susceptibility: a systematic review and meta-analysis of 52 studies. PLoS One 2014; 9 (03) e90090 . Doi: 10.1371/journal.pone.0090090
14 Brint E, O'Callaghan G, Houston A. Life in the Fas lane: differential outcomes of Fas signaling. Cell Mol Life Sci 2013; 70 (21) 4085-4099 . Doi: 10.1007/s00018-013-1327-z
15 Karakus S, Sancakdar E, Akkar O, Yildiz C, Demirpence O, Cetin A. Elevated serum CD95/FAS and HIF-1α levels, but not Tie-2 levels, may be biomarkers in patients with severe endometriosis: a preliminary report. J Minim Invasive Gynecol 2016; 23 (04) 573-577 . Doi: 10.1016/j.jmig.2016.01.025
16 Treloar SA, Wicks J, Nyholt DR. , et al. Genomewide linkage study in 1,176 affected sister pair families identifies a significant susceptibility locus for endometriosis on chromosome 10q26. Am J Hum Genet 2005; 77 (03) 365-376 . Doi: 10.1086/432960
17 Adachi S, Tajima A, Quan J. , 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
18 Nyholt DR, Low SK, Anderson CA. , et al. Genome-wide association meta-analysis identifies new endometriosis risk loci. Nat Genet 2012; 44 (12) 1355-1359 . Doi: 10.1038/ng.2445
19 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
20 Sundqvist J, Xu H, Vodolazkaia 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
21 Rahmioglu N, Montgomery GW, Zondervan KT. Genetics of endometriosis. Womens Health (Lond) 2015; 11 (05) 577-586 . Doi: 10.2217/whe.15.41
22 Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16 (03) 1215
23 Vetvicka V, Laganà AS, Salmeri FM. , et al. Regulation of apoptotic pathways during endometriosis: from the molecular basis to the future perspectives. Arch Gynecol Obstet 2016; 294 (05) 897-904 . Doi: 10.1007/s00404-016-4195-6
24 Orlando IC, Tanaka SCSV, Balarin MAS, da Silva SR, Pissetti CW. CASPASE-8 gene polymorphisms (rs13416436 and rs2037815) are not associated with preeclampsia development in Brazilian women. J Matern Fetal Neonatal Med 2018; 31 (03) 289-293 . Doi: 10.1080/14767058.2017.1285882
25 Camiña-Tato M, Fernández M, Morcillo-Suárez C. , et al. Genetic association of CASP8 polymorphisms with primary progressive multiple sclerosis. J Neuroimmunol 2010; 222 (1-2): 70-75 . Doi: 10.1016/j.jneuroim.2010.03.003
26 Rahmioglu N, Nyholt DR, Morris AP, Missmer SA, Montgomery GW, Zondervan KT. Genetic variants underlying risk of endometriosis: insights from meta-analysis of eight genome-wide association and replication datasets. Hum Reprod Update 2014; 20 (05) 702-716 . Doi: 10.1093/humupd/dmu015
27 Fernández RM, Noval JA, García-Lozano JC, Borrego S, Moliní JL, Antiñolo G. Polymorphisms in the promoter regions of FAS and FASL genes as candidate genetic factors conferring susceptibility to endometriosis. Int J Mol Med 2005; 15 (05) 865-869 . Doi: 10.3892/ijmm.15.5.865
28 Zhao ZZ, Nyholt DR, Le L, Treloar SA, Montgomery GW. Common variation in the CYP17A1 and IFIT1 genes on chromosome 10 does not contribute to the risk of endometriosis. Open Reprod Sci J 2008; 1: 35-40 . Doi: 10.2174/1874255600801010035
29 Montgomery GW, Nyholt DR, Zhao ZZ. , et al. The search for genes contributing to endometriosis risk. Hum Reprod Update 2008; 14 (05) 447-457 . Doi: 10.1093/humupd/dmn016