Functional analyses of endometriosis-related polymorphisms in the estrogen synthesis and metabolism-related genes.

Endometriosis is determined by genetic factors, and the prevalence of genetic polymorphisms varies greatly depending on the ethnic group studied. The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) of 9 genes involved in estrogen biosynthesi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hsin-Shih Wang, Hsien-Ming Wu, Bi-Hwa Cheng, Chih-Feng Yen, Pi-Yueh Chang, Angel Chao, Yun-Shien Lee, Hsien-Da Huang, Tzu-Hao Wang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6ffb3c0b4a614077823f368157b1aa00
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6ffb3c0b4a614077823f368157b1aa00
record_format	dspace
spelling	oai:doaj.org-article:6ffb3c0b4a614077823f368157b1aa002021-11-18T08:09:58ZFunctional analyses of endometriosis-related polymorphisms in the estrogen synthesis and metabolism-related genes.1932-620310.1371/journal.pone.0047374https://doaj.org/article/6ffb3c0b4a614077823f368157b1aa002012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23139742/?tool=EBIhttps://doaj.org/toc/1932-6203Endometriosis is determined by genetic factors, and the prevalence of genetic polymorphisms varies greatly depending on the ethnic group studied. The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) of 9 genes involved in estrogen biosynthesis and metabolism and the risks of endometriosis. Three hundred patients with endometriosis and 337 non-endometriotic controls were recruited. Thirty four non-synonymous SNPs, which change amino acid residues, were analyzed using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS). The functions of SNP-resulted amino acid changes were analyzed using multiple web-accessible databases and phosphorylation predicting algorithms. Among the 34 NCBI-listed SNPs, 22 did not exhibit polymorphism in this study of more than 600 Taiwanese Chinese women. However, homozygous and heterozygous mutants of 4 SNPs - rs6165 (genotype GG+GA, 307(Ala/Ala)+307(Ala/Thr)) of FSHR, rs 6166 (genotype GG+GA, 680(Ser/Asn)+680(Ser/Ser)) of FSHR, rs2066479 (genotype AA+AG, 289(Ser/Ser)+289(Ser/Gly)) of HSD17B3 and rs700519 (genotype TT+TC, 264(Cys/Cys)+264(Cys/Arg)) of CYP19, alone or in combination, were significantly associated with decreased risks of endometriosis. Bioinformatics results identified 307(Thr) of FSHR to be a site for O-linked glycosylation, 680(Ser) of FSHR a phosphorylated site by protein kinase B, and 289(Ser) of HSD17B3 a phosphorylated site by protein kinase B or ribosomal protein S6 kinase 1. Results of this study suggest that non-synonymous polymorphisms of FSHR, HSD17B3 and CYP19 genes may modulate the risk of endometriosis in Taiwanese Chinese women. Identification of the endometrosis-preferential non-synonymous SNPs and the conformational changes in those proteins may pave the way for the development of more disease-specific drugs.Hsin-Shih WangHsien-Ming WuBi-Hwa ChengChih-Feng YenPi-Yueh ChangAngel ChaoYun-Shien LeeHsien-Da HuangTzu-Hao WangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e47374 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hsin-Shih Wang Hsien-Ming Wu Bi-Hwa Cheng Chih-Feng Yen Pi-Yueh Chang Angel Chao Yun-Shien Lee Hsien-Da Huang Tzu-Hao Wang Functional analyses of endometriosis-related polymorphisms in the estrogen synthesis and metabolism-related genes.
description	Endometriosis is determined by genetic factors, and the prevalence of genetic polymorphisms varies greatly depending on the ethnic group studied. The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) of 9 genes involved in estrogen biosynthesis and metabolism and the risks of endometriosis. Three hundred patients with endometriosis and 337 non-endometriotic controls were recruited. Thirty four non-synonymous SNPs, which change amino acid residues, were analyzed using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS). The functions of SNP-resulted amino acid changes were analyzed using multiple web-accessible databases and phosphorylation predicting algorithms. Among the 34 NCBI-listed SNPs, 22 did not exhibit polymorphism in this study of more than 600 Taiwanese Chinese women. However, homozygous and heterozygous mutants of 4 SNPs - rs6165 (genotype GG+GA, 307(Ala/Ala)+307(Ala/Thr)) of FSHR, rs 6166 (genotype GG+GA, 680(Ser/Asn)+680(Ser/Ser)) of FSHR, rs2066479 (genotype AA+AG, 289(Ser/Ser)+289(Ser/Gly)) of HSD17B3 and rs700519 (genotype TT+TC, 264(Cys/Cys)+264(Cys/Arg)) of CYP19, alone or in combination, were significantly associated with decreased risks of endometriosis. Bioinformatics results identified 307(Thr) of FSHR to be a site for O-linked glycosylation, 680(Ser) of FSHR a phosphorylated site by protein kinase B, and 289(Ser) of HSD17B3 a phosphorylated site by protein kinase B or ribosomal protein S6 kinase 1. Results of this study suggest that non-synonymous polymorphisms of FSHR, HSD17B3 and CYP19 genes may modulate the risk of endometriosis in Taiwanese Chinese women. Identification of the endometrosis-preferential non-synonymous SNPs and the conformational changes in those proteins may pave the way for the development of more disease-specific drugs.
format	article
author	Hsin-Shih Wang Hsien-Ming Wu Bi-Hwa Cheng Chih-Feng Yen Pi-Yueh Chang Angel Chao Yun-Shien Lee Hsien-Da Huang Tzu-Hao Wang
author_facet	Hsin-Shih Wang Hsien-Ming Wu Bi-Hwa Cheng Chih-Feng Yen Pi-Yueh Chang Angel Chao Yun-Shien Lee Hsien-Da Huang Tzu-Hao Wang
author_sort	Hsin-Shih Wang
title	Functional analyses of endometriosis-related polymorphisms in the estrogen synthesis and metabolism-related genes.
title_short	Functional analyses of endometriosis-related polymorphisms in the estrogen synthesis and metabolism-related genes.
title_full	Functional analyses of endometriosis-related polymorphisms in the estrogen synthesis and metabolism-related genes.
title_fullStr	Functional analyses of endometriosis-related polymorphisms in the estrogen synthesis and metabolism-related genes.
title_full_unstemmed	Functional analyses of endometriosis-related polymorphisms in the estrogen synthesis and metabolism-related genes.
title_sort	functional analyses of endometriosis-related polymorphisms in the estrogen synthesis and metabolism-related genes.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/6ffb3c0b4a614077823f368157b1aa00
work_keys_str_mv	AT hsinshihwang functionalanalysesofendometriosisrelatedpolymorphismsintheestrogensynthesisandmetabolismrelatedgenes AT hsienmingwu functionalanalysesofendometriosisrelatedpolymorphismsintheestrogensynthesisandmetabolismrelatedgenes AT bihwacheng functionalanalysesofendometriosisrelatedpolymorphismsintheestrogensynthesisandmetabolismrelatedgenes AT chihfengyen functionalanalysesofendometriosisrelatedpolymorphismsintheestrogensynthesisandmetabolismrelatedgenes AT piyuehchang functionalanalysesofendometriosisrelatedpolymorphismsintheestrogensynthesisandmetabolismrelatedgenes AT angelchao functionalanalysesofendometriosisrelatedpolymorphismsintheestrogensynthesisandmetabolismrelatedgenes AT yunshienlee functionalanalysesofendometriosisrelatedpolymorphismsintheestrogensynthesisandmetabolismrelatedgenes AT hsiendahuang functionalanalysesofendometriosisrelatedpolymorphismsintheestrogensynthesisandmetabolismrelatedgenes AT tzuhaowang functionalanalysesofendometriosisrelatedpolymorphismsintheestrogensynthesisandmetabolismrelatedgenes
_version_	1718422114312126464

Functional analyses of endometriosis-related polymorphisms in the estrogen synthesis and metabolism-related genes.

Ejemplares similares