Association between col1a2 Polymorphism and the Occurrence of Pelvic Organ Prolapse in Brazilian Women

Abstract

Objective To evaluate the rs42524 polymorphism of the procollagen type I alpha (α) 2 (COL1A2) gene as a factor related to the development of pelvic organ prolapse (POP) in Brazilian women.

Methods The present study involved 112 women with POP stages III and IV (case group) and 180 women with POP stages zero and I (control group). Other clinical data were obtained by interviewing the patients about their medical history, and blood was also collected from the volunteers for the extraction of genomic DNA. The promoter region of the COL1A2 gene containing the rs42524 polymorphism was amplified, and the discrimination between the G and C variants was performed by digestion of the polymerase chain reaction (PCR) products with the MspA1I enzyme followed by agarose gel electrophoresis analysis.

Results A total of 292 women were analyzed. In the case group, 71 had the G/G genotype, 33 had the G/C genotype, and 7 had the C/C genotype. In turn, the ratio in the control group was 117 G/G, 51 G/C, and 11 C/C. There were no significant differences between the groups.

Conclusion Our data did not show an association between the COL1A2 polymorphism and the occurrence of POP.

Resumo

Objetivo Avaliar o polimorfismo rs42524 do gene pró-colágeno tipo I alfa (α) 2 (COL1A2) como fator relacionado ao desenvolvimento de prolapso de órgãos pélvicos (POP) em mulheres brasileiras.

Métodos O estudo envolveu 112 mulheres com POP nos estádios III e IV (grupo caso) e 180 mulheres com POP nos estádios zero e I (grupo controle). Outros dados clínicos foram obtidos por meio de entrevistas com as pacientes sobre seu histórico médico, e o sangue das voluntárias também foi coletado para extração de DNA genômico. A região promotora do gene COL1A2 contendo o polimorfismo rs42524 foi amplificada, e a discriminação entre as variantes G e C foi realizada por digestão dos produtos de reação em cadeia da polimerase (RCP) com a enzima MspA1I, seguida de análise por eletroforese em gel de agarose.

Resultados Foram analisadas 292 mulheres. No grupo caso, 71 tinham o genótipo G/G, 33 tinham o genótipo G/C, e 7 tinham o genótipo C/C. Por sua vez, a relação no grupo controle foi de 117 G/G, 51 G/C e 11 C/C. Não houve diferenças significativas entre os grupos.

Conclusão Nossos dados não mostraram associação do polimorfismo do gene COL1A2 com a ocorrência de POP.

Keywords

procollagen type I alpha (α) 2 gene - polymorphism - pelvic organ prolapse

Palavras-chave

gene pró-colágeno tipo I alfa (α) 2 - polimorfismo - prolapso de órgãos pélvicos

Contributors

Rosa J. P. F., Haddad R. F., Maeda F. G. R., Souto R. P., Fernandes C. E. and Oliveira E. contributed with the project and the 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 Haylen BT, Maher CF, Barber MD. , et al. An International Urogynecological Association (IUGA) / International Continence Society (ICS) Joint Report on the Terminology for Female Pelvic Organ Prolapse (POP). Neurourol Urodyn 2016; 35 (02) 137-168 . Doi: 10.1002/nau.22922
• 2 Lince SL, van Kempen LC, Vierhout ME, Kluivers KB. A systematic review of clinical studies on hereditary factors in pelvic organ prolapse. Int Urogynecol J Pelvic Floor Dysfunct 2012; 23 (10) 1327-1336 . Doi: 10.1007/s00192-012-1704-4
• 3 Wang X, Li Y, Chen J, Guo X, Guan H, Li C. Differential expression profiling of matrix metalloproteinases and tissue inhibitors of metalloproteinases in females with or without pelvic organ prolapse. Mol Med Rep 2014; 10 (04) 2004-2008 . Doi: 10.3892/mmr.2014.2467
• 4 Ferrari MM, Rossi G, Biondi ML, Viganò P, Dell'utri C, Meschia M. Type I collagen and matrix metalloproteinase 1, 3 and 9 gene polymorphisms in the predisposition to pelvic organ prolapse. Arch Gynecol Obstet 2012; 285 (06) 1581-1586 . Doi: 10.1007/s00404-011-2199-9
• 5 Swift SE, Pound T, Dias JK. Case-control study of etiologic factors in the development of severe pelvic organ prolapse. Int Urogynecol J Pelvic Floor Dysfunct 2001; 12 (03) 187-192 . Doi: 10.1007/s001920170062
• 6 Bortolini MA, Rizk DE. Genetics of pelvic organ prolapse: crossing the bridge between bench and bedside in urogynecologic research. Int Urogynecol J Pelvic Floor Dysfunct 2011; 22 (10) 1211-1219 . Doi: 10.1007/s00192-011-1502-4
• 7 Skorupski P, Jankiewicz K, Miotła P, Marczak M, Kulik-Rechberger B, Rechberger T. The polymorphisms of the MMP-1 and the MMP-3 genes and the risk of pelvic organ prolapse. Int Urogynecol J Pelvic Floor Dysfunct 2013; 24 (06) 1033-1038 . Doi: 10.1007/s00192-012-1970-1
• 8 de Wet W, Bernard M, Benson-Chanda V. , et al. Organization of the human pro-alpha 2(I) collagen gene. J Biol Chem 1987; 262 (33) 16032-16036
• 9 Kataoka K, Ogura E, Hasegawa K. , et al. Mutations in type I collagen genes in Japanese osteogenesis imperfecta patients. Pediatr Int 2007; 49 (05) 564-569
• 10 De Vos A, Sermon K, Van de Velde H. , et al. Two pregnancies after preimplantation genetic diagnosis for osteogenesis imperfecta type I and type IV. Hum Genet 2000; 106 (06) 605-613 . Doi: 10.1007/s004390000298
• 11 Alanay Y, Avaygan H, Camacho N. , et al. Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. Am J Hum Genet 2010; 86 (04) 551-559 . Doi: 10.1016/j.ajhg.2010.02.022
• 12 Cole WG. The Nicholas Andry Award-1996. The molecular pathology of osteogenesis imperfecta. Clin Orthop Relat Res 1997; (343) 235-248
• 13 Byers PH, Wallis GA, Willing MC. Osteogenesis imperfecta: translation of mutation to phenotype. J Med Genet 1991; 28 (07) 433-442 . Doi: 10.1136/jmg.28.7.433
• 14 Romero AA, Jamison MG, Weidner AC. Are single nucleotide polymorphisms associated with pelvic organ prolapse?. J Pelvic Med Surg 2008; 14 (01) 37-43 . Doi: 10.1097/SPV.0b013e3181637a49
• 15 Gajko-Galicka A. Mutations in type I collagen genes resulting in osteogenesis imperfecta in humans. Acta Biochim Pol 2002; 49 (02) 433-441
• 16 Meng Q, Hao Q, Zhao C. The association between collagen gene polymorphisms and intracranial aneurysms: a meta-analysis. Neurosurg Rev 2017; ••• DOI: 10.1007/s10143-017-0925-x.
• 17 Majchrzycki M, Bartkowiak-Wieczorek J, Bogacz A. , et al. The importance of polymorphic variants of collagen 1A2 gene (COL1A2) in the development of osteopenia and osteoporosis in postmenopausal women. Ginekol Pol 2017; 88 (08) 414-420 . Doi: 10.5603/GP.a2017.0077
• 18 Lindahl K, Rubin CJ, Brändström H. , et al. Heterozygosity for a coding SNP in COL1A2 confers a lower BMD and an increased stroke risk. Biochem Biophys Res Commun 2009; 384 (04) 501-505 . Doi: 10.1016/j.bbrc.2009.05.006
• 19 Gan Q, Liu Q, Hu X, You C. Collagen type I alpha 2 (COL1A2) Polymorphism contributes to intracranial aneurysm susceptibility: a meta-analysis. Med Sci Monit 2017; 23: 3240-3246 . Doi: 10.12659/msm.902327
• 20 Instituto Brasileiro de Geografia e Estatística. Fundo de População das Nações Unidas. Indicadores Sociodemográficos Prospectivos para o Brasil 1991–2030. Rio de Janeiro, RJ: Arbeit; 2006. http://www.ibge.gov.br/home/estatistica/populacao/projecao_da_populacao/publicacao_UNFPA.pdf . Accessed July 22, 2017
• 21 Subak LL, Waetjen LE, van den Eeden S, Thom DH, Vittinghoff E, Brown JS. Cost of pelvic organ prolapse surgery in the United States. Obstet Gynecol 2001; 98 (04) 646-651 . Doi: 10.1016/S0029-7844(01)01472-7
• 22 Bump RC, Mattiasson A, Bø K. , et al. The standardization of terminology of female pelvic organ prolapse and pelvic floor dysfunction. Am J Obstet Gynecol 1996; 175 (01) 10-17 . Doi: 10.1016/S0002-9378(96)70243-0
• 23 Liu W, Pang B, Lu M. , et al. The rs42524 COL1A2 polymorphism is associated with primary intracerebral hemorrhage in a Chinese population. J Clin Neurosci 2012; 19 (12) 1711-1714 . Doi: 10.1016/j.jocn.2012.03.025
• 24 Rodrigues AM, Girão MJ, da Silva ID, Sartori MG, Martins KdeF, Castro RdeA. COL1A1 Sp1-binding site polymorphism as a risk factor for genital prolapse. Int Urogynecol J Pelvic Floor Dysfunct 2008; 19 (11) 1471-1475 . Doi: 10.1007/s00192-008-0662-3
• 25 Feiner B, Fares F, Azam N, Auslender R, David M, Abramov Y. Does COLIA1 SP1-binding site polymorphism predispose women to pelvic organ prolapse?. Int Urogynecol J Pelvic Floor Dysfunct 2009; 20 (09) 1061-1065 . Doi: 10.1007/s00192-009-0895-9
• 26 Yoneyama T, Kasuya H, Onda H. , et al. Collagen type I alpha2 (COL1A2) is the susceptible gene for intracranial aneurysms. Stroke 2004; 35 (02) 443-448 . Doi: 10.1161/01.STR.0000110788.45858.DC