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...
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| Veröffentlicht in: | PloS one 2012-11, Vol.7 (11), p.e47374-e47374 |
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| creator | Wang, Hsin-Shih Wu, Hsien-Ming Cheng, Bi-Hwa Yen, Chih-Feng Chang, Pi-Yueh Chao, Angel Lee, Yun-Shien Huang, Hsien-Da Wang, Tzu-Hao |
| 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. |
| doi_str_mv | 10.1371/journal.pone.0047374 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0047374</identifier><identifier>PMID: 23139742</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Adult ; AKT protein ; Algorithms ; Amino Acid Sequence ; Amino acids ; Analysis ; Androgens ; Aromatase ; Aromatase - genetics ; Asian Continental Ancestry Group - genetics ; Bioinformatics ; Biology ; Biosynthesis ; China ; Chromosomes ; Cytochrome ; Cytochrome P-450 ; Dehydrogenases ; Demography ; Development and progression ; Drug development ; Drugs ; Endocrinology ; Endometriosis ; Endometriosis - blood ; Endometriosis - genetics ; Endometriosis - metabolism ; Endometriosis - surgery ; Enzymes ; Estradiol - blood ; Estradiol Dehydrogenases - genetics ; Estrogen ; Estrogens ; Estrogens - biosynthesis ; Estrogens - genetics ; Female ; Gene Frequency - genetics ; Gene Regulatory Networks - genetics ; Genes ; Genetic aspects ; Genetic factors ; Genetic Predisposition to Disease ; Genotype & phenotype ; Glycosylation ; Gynecology ; Haplotypes - genetics ; Health risks ; Homozygote ; Hospitals ; Humans ; Infertility ; Ionization ; Kinases ; Laboratories ; Mass spectrometry ; Mass spectroscopy ; Mathematics ; Medicine ; Metabolism ; Middle Aged ; Minority & ethnic groups ; Molecular Sequence Data ; Mutants ; Mutation - genetics ; Obstetrics ; Phenols (Class of compounds) ; Phosphorylation ; Physiological aspects ; Polymorphism ; Polymorphism, Single Nucleotide - genetics ; Protein kinases ; Proteins ; Receptors, FSH - chemistry ; Receptors, FSH - genetics ; Ribosomal protein S6 ; Ribosomal protein S6 kinase ; Risk Factors ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Young Adult</subject><ispartof>PloS one, 2012-11, Vol.7 (11), p.e47374-e47374</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Wang et al 2012 Wang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-30bfd8d2f52f0c50a5b5abef0285ac9ff8722290587aa2bd4b6afd7df7f4057d3</citedby><cites>FETCH-LOGICAL-c692t-30bfd8d2f52f0c50a5b5abef0285ac9ff8722290587aa2bd4b6afd7df7f4057d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490981/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490981/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23139742$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Lobaccaro, Jean-Marc A.</contributor><creatorcontrib>Wang, Hsin-Shih</creatorcontrib><creatorcontrib>Wu, Hsien-Ming</creatorcontrib><creatorcontrib>Cheng, Bi-Hwa</creatorcontrib><creatorcontrib>Yen, Chih-Feng</creatorcontrib><creatorcontrib>Chang, Pi-Yueh</creatorcontrib><creatorcontrib>Chao, Angel</creatorcontrib><creatorcontrib>Lee, Yun-Shien</creatorcontrib><creatorcontrib>Huang, Hsien-Da</creatorcontrib><creatorcontrib>Wang, Tzu-Hao</creatorcontrib><title>Functional analyses of endometriosis-related polymorphisms in the estrogen synthesis and metabolism-related genes</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Acids</subject><subject>Adult</subject><subject>AKT protein</subject><subject>Algorithms</subject><subject>Amino Acid Sequence</subject><subject>Amino acids</subject><subject>Analysis</subject><subject>Androgens</subject><subject>Aromatase</subject><subject>Aromatase - genetics</subject><subject>Asian Continental Ancestry Group - genetics</subject><subject>Bioinformatics</subject><subject>Biology</subject><subject>Biosynthesis</subject><subject>China</subject><subject>Chromosomes</subject><subject>Cytochrome</subject><subject>Cytochrome P-450</subject><subject>Dehydrogenases</subject><subject>Demography</subject><subject>Development and progression</subject><subject>Drug development</subject><subject>Drugs</subject><subject>Endocrinology</subject><subject>Endometriosis</subject><subject>Endometriosis - blood</subject><subject>Endometriosis - genetics</subject><subject>Endometriosis - metabolism</subject><subject>Endometriosis - surgery</subject><subject>Enzymes</subject><subject>Estradiol - blood</subject><subject>Estradiol Dehydrogenases - genetics</subject><subject>Estrogen</subject><subject>Estrogens</subject><subject>Estrogens - biosynthesis</subject><subject>Estrogens - genetics</subject><subject>Female</subject><subject>Gene Frequency - genetics</subject><subject>Gene Regulatory Networks - genetics</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic factors</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype & phenotype</subject><subject>Glycosylation</subject><subject>Gynecology</subject><subject>Haplotypes - genetics</subject><subject>Health risks</subject><subject>Homozygote</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Infertility</subject><subject>Ionization</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Mathematics</subject><subject>Medicine</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Minority & ethnic groups</subject><subject>Molecular Sequence Data</subject><subject>Mutants</subject><subject>Mutation - genetics</subject><subject>Obstetrics</subject><subject>Phenols (Class of compounds)</subject><subject>Phosphorylation</subject><subject>Physiological aspects</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Protein kinases</subject><subject>Proteins</subject><subject>Receptors, FSH - chemistry</subject><subject>Receptors, FSH - genetics</subject><subject>Ribosomal protein S6</subject><subject>Ribosomal protein S6 kinase</subject><subject>Risk Factors</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QLgujFjPlokvZGWBZXBxYW_LoNp00ykyFtZpNWnH9v6nSHqeyFFPqRPu-T5jQny15itMRU4A9bP4QO3HLnO71EqBBUFI-yc1xRsuAE0ccn92fZsxi3CDFacv40OyMU00oU5Dy7ux66prc-mXJIp33UMfcm153yre6D9dHGRdAOeq3ynXf71ofdxsY25rbL-43OdeyDX-suj_suPSc-mVSe0lB7l8hjPEE6Ps-eGHBRv5iuF9mP60_fr74sbm4_r64ubxYNr0i_oKg2qlTEMGJQwxCwmkGtDSIlg6YyphSEkAqxUgCQWhU1B6OEMsIUiAlFL7LXB-_O-SinakWJKeGCMCxoIlYHQnnYyl2wLYS99GDl3wEf1hJCbxunJTempg2qC-C4QEKUhBrKS8xEjQEQSq6P02xD3WrV6K4P4GbS-ZvObuTa_5K0qFBV4iR4NwmCvxtSTWVrY6Odg077IX03ZhhRzniZ0Df_oA-vbqLWkBZgO-PTvM0olZeFEKiitBxdyweodCjd2iZtLWPT-CzwfhZITK9_92sYYpSrb1__n739OWffnrAbDa7fRO-GcW_GOVgcwCb4GIM2xyJjJMfOuK-GHDtDTp2RYq9Of9AxdN8K9A8hwAuD</recordid><startdate>20121106</startdate><enddate>20121106</enddate><creator>Wang, Hsin-Shih</creator><creator>Wu, Hsien-Ming</creator><creator>Cheng, Bi-Hwa</creator><creator>Yen, Chih-Feng</creator><creator>Chang, Pi-Yueh</creator><creator>Chao, Angel</creator><creator>Lee, Yun-Shien</creator><creator>Huang, Hsien-Da</creator><creator>Wang, Tzu-Hao</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20121106</creationdate><title>Functional analyses of endometriosis-related polymorphisms in the estrogen synthesis and metabolism-related genes</title><author>Wang, Hsin-Shih ; Wu, Hsien-Ming ; Cheng, Bi-Hwa ; Yen, Chih-Feng ; Chang, Pi-Yueh ; Chao, Angel ; Lee, Yun-Shien ; Huang, Hsien-Da ; Wang, Tzu-Hao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-30bfd8d2f52f0c50a5b5abef0285ac9ff8722290587aa2bd4b6afd7df7f4057d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Acids</topic><topic>Adult</topic><topic>AKT protein</topic><topic>Algorithms</topic><topic>Amino Acid Sequence</topic><topic>Amino acids</topic><topic>Analysis</topic><topic>Androgens</topic><topic>Aromatase</topic><topic>Aromatase - genetics</topic><topic>Asian Continental Ancestry Group - genetics</topic><topic>Bioinformatics</topic><topic>Biology</topic><topic>Biosynthesis</topic><topic>China</topic><topic>Chromosomes</topic><topic>Cytochrome</topic><topic>Cytochrome P-450</topic><topic>Dehydrogenases</topic><topic>Demography</topic><topic>Development and progression</topic><topic>Drug development</topic><topic>Drugs</topic><topic>Endocrinology</topic><topic>Endometriosis</topic><topic>Endometriosis - blood</topic><topic>Endometriosis - genetics</topic><topic>Endometriosis - metabolism</topic><topic>Endometriosis - surgery</topic><topic>Enzymes</topic><topic>Estradiol - blood</topic><topic>Estradiol Dehydrogenases - genetics</topic><topic>Estrogen</topic><topic>Estrogens</topic><topic>Estrogens - biosynthesis</topic><topic>Estrogens - genetics</topic><topic>Female</topic><topic>Gene Frequency - genetics</topic><topic>Gene Regulatory Networks - genetics</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic factors</topic><topic>Genetic Predisposition to Disease</topic><topic>Genotype & phenotype</topic><topic>Glycosylation</topic><topic>Gynecology</topic><topic>Haplotypes - genetics</topic><topic>Health risks</topic><topic>Homozygote</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Infertility</topic><topic>Ionization</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Mathematics</topic><topic>Medicine</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Minority & ethnic groups</topic><topic>Molecular Sequence Data</topic><topic>Mutants</topic><topic>Mutation - genetics</topic><topic>Obstetrics</topic><topic>Phenols (Class of compounds)</topic><topic>Phosphorylation</topic><topic>Physiological aspects</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Protein kinases</topic><topic>Proteins</topic><topic>Receptors, FSH - chemistry</topic><topic>Receptors, FSH - genetics</topic><topic>Ribosomal protein S6</topic><topic>Ribosomal protein S6 kinase</topic><topic>Risk Factors</topic><topic>Single nucleotide polymorphisms</topic><topic>Single-nucleotide polymorphism</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Hsin-Shih</creatorcontrib><creatorcontrib>Wu, Hsien-Ming</creatorcontrib><creatorcontrib>Cheng, Bi-Hwa</creatorcontrib><creatorcontrib>Yen, Chih-Feng</creatorcontrib><creatorcontrib>Chang, Pi-Yueh</creatorcontrib><creatorcontrib>Chao, Angel</creatorcontrib><creatorcontrib>Lee, Yun-Shien</creatorcontrib><creatorcontrib>Huang, Hsien-Da</creatorcontrib><creatorcontrib>Wang, Tzu-Hao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Hsin-Shih</au><au>Wu, Hsien-Ming</au><au>Cheng, Bi-Hwa</au><au>Yen, Chih-Feng</au><au>Chang, Pi-Yueh</au><au>Chao, Angel</au><au>Lee, Yun-Shien</au><au>Huang, Hsien-Da</au><au>Wang, Tzu-Hao</au><au>Lobaccaro, Jean-Marc A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional analyses of endometriosis-related polymorphisms in the estrogen synthesis and metabolism-related genes</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-11-06</date><risdate>2012</risdate><volume>7</volume><issue>11</issue><spage>e47374</spage><epage>e47374</epage><pages>e47374-e47374</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23139742</pmid><doi>10.1371/journal.pone.0047374</doi><tpages>e47374</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-11, Vol.7 (11), p.e47374-e47374 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1326725173 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acids Adult AKT protein Algorithms Amino Acid Sequence Amino acids Analysis Androgens Aromatase Aromatase - genetics Asian Continental Ancestry Group - genetics Bioinformatics Biology Biosynthesis China Chromosomes Cytochrome Cytochrome P-450 Dehydrogenases Demography Development and progression Drug development Drugs Endocrinology Endometriosis Endometriosis - blood Endometriosis - genetics Endometriosis - metabolism Endometriosis - surgery Enzymes Estradiol - blood Estradiol Dehydrogenases - genetics Estrogen Estrogens Estrogens - biosynthesis Estrogens - genetics Female Gene Frequency - genetics Gene Regulatory Networks - genetics Genes Genetic aspects Genetic factors Genetic Predisposition to Disease Genotype & phenotype Glycosylation Gynecology Haplotypes - genetics Health risks Homozygote Hospitals Humans Infertility Ionization Kinases Laboratories Mass spectrometry Mass spectroscopy Mathematics Medicine Metabolism Middle Aged Minority & ethnic groups Molecular Sequence Data Mutants Mutation - genetics Obstetrics Phenols (Class of compounds) Phosphorylation Physiological aspects Polymorphism Polymorphism, Single Nucleotide - genetics Protein kinases Proteins Receptors, FSH - chemistry Receptors, FSH - genetics Ribosomal protein S6 Ribosomal protein S6 kinase Risk Factors Single nucleotide polymorphisms Single-nucleotide polymorphism Young Adult |
| title | Functional analyses of endometriosis-related polymorphisms in the estrogen synthesis and metabolism-related genes |
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