Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Assisted Reproduction and Genetics
Published in: Journal of Assisted Reproduction and Genetics 9/2015

01-09-2015 | Genetics

Association of WNT4 polymorphisms with endometriosis in infertile patients

Authors: Fernanda Mafra, Michele Catto, Bianca Bianco, Caio Parente Barbosa, Denise Christofolini

Published in: Journal of Assisted Reproduction and Genetics | Issue 9/2015

Login to get access

Abstract

Purpose

Recently, several genome-wide association studies have demonstrated an association between endometriosis and markers located in or near to WNT4 gene. In order to assess the validity of the findings, we conducted a replication case–control study in a Brazilian population.

Methods

Genetic association study comprising 400 infertile women with endometriosis and 400 fertile women as controls. TaqMan allelic discrimination technique was used to investigate the relationship between endometriosis and four single-nucleotide polymorphisms (rs16826658, rs3820282, rs2235529, and rs7521902) in WNT4 gene. Genotype distribution, allele frequency, and haplotype analysis of the WNT4 polymorphisms were performed. A p value <0.05 was considered significant.

Results

The results revealed a significant association of rs16826658 (p = 7e-04) and rs3820282 (p = 0.048) single-nucleotide polymorphisms (SNPs) on WNT4 gene with endometriosis-related infertility, while rs2235529 and rs7521902 SNPs showed no difference between cases and controls.

Conclusions

Our results suggested that rs16826658 and rs3820282 polymorphisms on WNT4 gene might be involved in the pathogenesis of endometriosis in the infertile women studied. Analysis of WNT4 genetic variants might help to identify patients at high risk for disease development.
Literature
1.
Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20:781–810.CrossRefPubMed
2.
3.
Li Q, Kannan A, Das A, Demayo FJ, Hornsby PJ, Young SL, et al. WNT4 acts downstream of BMP2 and functions via beta-catenin signaling pathway to regulate human endometrial stromal cell differentiation. Endocrinology. 2013;154(1):446–57.PubMedCentralCrossRefPubMed
4.
Vainio S, Heikkilä M, Kispert A, Chin N, McMahon AP. Female development in mammals is regulated by Wnt-4 signalling. Nature. 1999;397(6718):405–9.CrossRefPubMed
5.
Boyer A, Lapointe E, Zheng X, Cowan RG, Li H, Quirk SM, et al. WNT4 is required for normal ovarian follicle development and female fertility. FASEB J. 2010;24:3010–25.PubMedCentralCrossRefPubMed
6.
Jordan BK, Mohammed M, Ching ST, Délot E, Chen XN, Dewing P, et al. Up-regulation of WNT-4 signaling and dosage-sensitive sex reversal in humans. Am J Hum Genet. 2001;68(5):1102–9.PubMedCentralCrossRefPubMed
7.
Else T, Hammer GD. Genetic analysis of adrenal absence: agenesis and aplasia. Trends Endocrinol Metab. 2005;16:458–68.CrossRefPubMed
8.
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;42:707–10.CrossRefPubMed
9.
10.
Nyholt DR, Low K, Anderson A, Painter JN, Uno S, Morris AP, et al. Genome-wide association meta-analysis identifies new endometriosis risk loci. Nat Genet. 2012;44:1355–9.PubMedCentralCrossRefPubMed
11.
Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997;67:817–21.
12.
Barbosa CP, Souza AM, Bianco B, Christofolini D, Bach FA, Lima GR. Frequency of endometriotic lesions in peritoneum samples from asymptomatic fertile women and correlation with CA125 values. Sao Paulo Med J. 2009;127(6):342–5.CrossRefPubMed
13.
14.
15.
16.
Dun EC, Taylor RN, Wieser F. Advances in the genetics of endometriosis. Genome Med. 2010;14(2):75.CrossRef
17.
Aznaurova YB, Zhumataev MB, Roberts TK, Aliper AM, Zhavoronkov AA. Molecular aspects of development and regulation of endometriosis. Reprod Biol Endocrinol. 2014;13(12):50.CrossRef
18.
Lee GH, Choi YM, Hong MA, Yoon SH, Kim JJ, Hwang K, et al. Association of CDKN2BAS and WNT4 genetic polymorphisms in Korean patients with endometriosis. Fertil Steril. 2014;102(5):1393–7.CrossRefPubMed
19.
Wu Z, Yuan M, Li Y, Fu F, Ma W, Li H, et al. Analysis of WNT4 polymorphism in Chinese Han women with endometriosis. Reprod Biomed Online. 2015;30(4):415–20.CrossRefPubMed
20.
Luong HT, Painter JN, Shakhbazov K, Chapman B, Henders AK, Powell JE, et al. Fine mapping of variants associated with endometriosis in the WNT4 region on chromosome 1p36. Mol Epidemiol Genet. 2013;4(4):193–206.
21.
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(1):51–4.PubMedCentralCrossRefPubMed
22.
Pagliardini L, Gentilini D, Vigano P, Panina-Bordignon P, Busacca M, Candiani M, et al. An Italian association study and meta-analysis with previous GWAS confirm WNT4, CDKN2BAS and FN1 as the first identified susceptibility loci for endometriosis. J Med Genet. 2013;50(1):43–6.CrossRefPubMed
23.
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(3):835–9.CrossRefPubMed
24.
Giolo SR, Soler JM, Greenway SC, Almeida MA, de Andrade M, Seidman JG, et al. Brazilian urban population genetics structure reveals a high degree of admixture. Eur J Hum Genet. 2012;20(1):111–6.PubMedCentralCrossRefPubMed
25.
Franco HL, Dai D, Lee KY, Rubel CA, Roop D, Boerboom D, et al. WNT4 is a key regulator of normal postnatal uterine development and progesterone signaling during embryo implantation and decidualization in the mouse. FASEB J. 2011;25(4):1176–87.PubMedCentralCrossRefPubMed
26.
Biason-Lauber A, De Filippo G, Konrad D, Scarano G, Nazzaro A, Schoenle EJ. WNT4 deficiency—a clinical phenotype distinct from the classic Mayer–Rokitansky–Kuster–Hauser syndrome: a case report. Hum Reprod. 2007;22(1):224–9.CrossRefPubMed
27.
Philibert P, Biason-Lauber A, Rouzier R, Pienkowski C, Paris F, Konrad D, et al. Identification and functional analysis of a new WNT4 gene mutation among 28 adolescent girls with primary amenorrhea and mullerian duct abnormalities: a French collaborative study. J Clin Endocrinol Metab. 2008;93(3):895–900.CrossRefPubMed
28.
29.
Bui TD, Zhang L, Rees MCP, Bicknell R, Harris AL. Expression and hormone regulation of Wnt2, 3, 4, 5a, 7a, 7b and 10b in normal human endometrium and endometrial carcinoma. Br J Cancer. 1997;75:1131–6.PubMedCentralCrossRefPubMed
30.
Gaetje R, Holtrich U, Engels K, Kissler S, Rody A, Karn T, et al. Endometriosis may be generated by mimicking the ontogenetic development of the female genital tract. Fertil Steril. 2007;87:651–6.CrossRefPubMed
31.
Pabona JM, Simmen FA, Nikiforov MA, Zhuang D, Shankar K, Velarde MC, et al. Kruppel-like factor 9 and progesterone receptor coregulation of decidualizing endometrial stromal cells: implications for the pathogenesis of endometriosis. J Clin Endocrinol Metab. 2012;97(3):376–92.CrossRef
Metadata
Title
Association of WNT4 polymorphisms with endometriosis in infertile patients
Authors
Fernanda Mafra
Michele Catto
Bianca Bianco
Caio Parente Barbosa
Denise Christofolini
Publication date
01-09-2015
Publisher
Springer US
Published in
Journal of Assisted Reproduction and Genetics / Issue 9/2015
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-015-0523-1

Other articles of this Issue 9/2015

Journal of Assisted Reproduction and Genetics 9/2015 Go to the issue

Reproductive Physiology and Disease

Antimullerian hormone levels are inversely associated with body mass index (BMI) in women with polycystic ovary syndrome

Reproductive Physiology and Disease

Dexamethasone attenuates the embryotoxic effect of endometriotic peritoneal fluid in a murine model

Embryo Biology

Reduced blastocyst formation in reduced culture volume

Erratum

Erratum to: Birth defects and congenital health risks in children conceived through assisted reproduction technology (ART): a meeting report

Genetics

Association between IL-6 −174 G/C, IL-6 −634 G/C, and IFN-γ +874 A/T polymorphisms and susceptibility to recurrent pregnancy loss: a meta-analysis

Case Report

Birth of nine normal healthy babies following transfer of blastocysts derived from human single-pronucleate zygotes