Loading…
The R453Q and D151A polymorphisms of Hexose-6-Phosphate Dehydrogenase Gene (H6PD) influence the polycystic ovary syndrome (PCOS) and obesity
Hexose-6-phosphate dehydrogenase (H6PDH) influences 11β-hydroxysteroid dehydrogenase activity, a key enzyme in the peripheral metabolism of cortisol that modulates insulin sensitivity in adipose tissue. To study the associations of R453Q and D151A polymorphisms in the H6PDH gene (H6PD) with polycyst...
Saved in:
| Published in: | Gene 2012-04, Vol.497 (1), p.38-44 |
|---|---|
| Main Authors: | , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c379t-7c1f938772c9c2c6d90781d97d97b4115edbdac5ec2a843f68127479da832f2a3 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c379t-7c1f938772c9c2c6d90781d97d97b4115edbdac5ec2a843f68127479da832f2a3 |
| container_end_page | 44 |
| container_issue | 1 |
| container_start_page | 38 |
| container_title | Gene |
| container_volume | 497 |
| creator | Martínez-García, M.A. San-Millán, J.L. Escobar-Morreale, H.F. |
| description | Hexose-6-phosphate dehydrogenase (H6PDH) influences 11β-hydroxysteroid dehydrogenase activity, a key enzyme in the peripheral metabolism of cortisol that modulates insulin sensitivity in adipose tissue. To study the associations of R453Q and D151A polymorphisms in the H6PDH gene (H6PD) with polycystic ovary syndrome (PCOS) and their influence on clinical and metabolic variables, we genotyped 237 patients with PCOS and 135 control women for the R453Q (rs6688832) and D151A (rs34603401) variants in H6PD. The R453Q genotypes were distributed differently in patients and controls (χ2=9.55, P=0.002). Genotypes of D151A were distributed evenly in women with PCOS and controls, but showed a different distribution in non-obese and obese women (χ2=3.95, P=0.047), especially within the PCOS subgroup (χ2=4.65, P=0.031). A backward stepwise likelihood ratio logistic regression model (Nagelkerke's R2=0.490; χ2=164; P |
| doi_str_mv | 10.1016/j.gene.2012.01.047 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_926645693</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S037811191200090X</els_id><sourcerecordid>926645693</sourcerecordid><originalsourceid>FETCH-LOGICAL-c379t-7c1f938772c9c2c6d90781d97d97b4115edbdac5ec2a843f68127479da832f2a3</originalsourceid><addsrcrecordid>eNp9kc1u1DAUhS0EotPCC7AA76CLBP8kcSyxqWagg1SpA23Xlse-aTyaxKmdqcg79KFxmMISy5I33zm-9xyE3lGSU0Krz7v8HnrIGaEsJzQnhXiBFrQWMiOE1y_RgnBRZ5RSeYJOY9yRdMqSvUYnjHFScSYW6Om2BfyzKPkPrHuLV7SkF3jw-6nzYWhd7CL2DV7DLx8hq7JN6-PQ6hHwCtrJBp8m0BHwZRoEf1pXm9U5dn2zP0BvAI_Je_YyUxydwf5RhwnHqU-6LuGb5fXN-Z9v_RaiG6c36FWj9xHePr9n6O7b19vlOru6vvy-vLjKDBdyzIShjeS1EMxIw0xlJRE1tVKkuy0oLcFurTYlGKbrgjdVTZkohLS65qxhmp-hj0ffIfiHA8RRdS4a2O91D_4QlWRVVZSV5IlkR9IEH2OARg3BdWkNRYmaS1A7NZeg5hIUoSqVkETvn-0P2w7sP8nf1BPw4Qg02it9H1xUdzfJoUwFcSHKmfhyJCDF8OggqGjcnKl1AcyorHf_m-A34oCgQg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>926645693</pqid></control><display><type>article</type><title>The R453Q and D151A polymorphisms of Hexose-6-Phosphate Dehydrogenase Gene (H6PD) influence the polycystic ovary syndrome (PCOS) and obesity</title><source>Elsevier:Jisc Collections:Elsevier Read and Publish Agreement 2022-2024:Freedom Collection (Reading list)</source><creator>Martínez-García, M.A. ; San-Millán, J.L. ; Escobar-Morreale, H.F.</creator><creatorcontrib>Martínez-García, M.A. ; San-Millán, J.L. ; Escobar-Morreale, H.F.</creatorcontrib><description>Hexose-6-phosphate dehydrogenase (H6PDH) influences 11β-hydroxysteroid dehydrogenase activity, a key enzyme in the peripheral metabolism of cortisol that modulates insulin sensitivity in adipose tissue. To study the associations of R453Q and D151A polymorphisms in the H6PDH gene (H6PD) with polycystic ovary syndrome (PCOS) and their influence on clinical and metabolic variables, we genotyped 237 patients with PCOS and 135 control women for the R453Q (rs6688832) and D151A (rs34603401) variants in H6PD. The R453Q genotypes were distributed differently in patients and controls (χ2=9.55, P=0.002). Genotypes of D151A were distributed evenly in women with PCOS and controls, but showed a different distribution in non-obese and obese women (χ2=3.95, P=0.047), especially within the PCOS subgroup (χ2=4.65, P=0.031). A backward stepwise likelihood ratio logistic regression model (Nagelkerke's R2=0.490; χ2=164; P<0.0001) retained free testosterone (OR=1.13; 95% CI: 1.10–1.17) and H6PD Q453 alleles (OR=0.46; 95% CI: 0.27–0.79) as statistically significant predictors for PCOS, whereas homeostasis model assessment of insulin resistance and the H6PD D151A variant were excluded by the model. Both H6PD variants were associated with several phenotypic variables, including fasting insulin, homeostasis model assessment of insulin resistance and androstenedione levels. In summary, the R453Q and D151A variants of the H6PD gene are associated with PCOS and obesity, respectively, and may contribute to the PCOS phenotype by influencing obesity, insulin resistance and hyperandrogenism.
► Hexose-6-phosphate dehydrogenase influences peripheral cortisol metabolism. ► Hexose-6-phosphate dehydrogenase is encoded by H6PD. ► Q alleles of the R453Q variant in H6PD protect against PCOS. ► A alleles of the D151A variant in H6PD are associated with obesity. ► H6PD R453Q and D151A variants influence insulin resistance and hyperandrogenism.</description><identifier>ISSN: 0378-1119</identifier><identifier>EISSN: 1879-0038</identifier><identifier>DOI: 10.1016/j.gene.2012.01.047</identifier><identifier>PMID: 22306327</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>adipose tissue ; Adrenal androgens ; Adult ; alleles ; Androgen excess ; androstenedione ; animal ovaries ; Carbohydrate Dehydrogenases - genetics ; cortisol ; fasting ; Female ; Genotype ; homeostasis ; Humans ; hyperandrogenism ; Hyperandrogenism - genetics ; insulin ; Insulin resistance ; Insulin Resistance - genetics ; Metabolism ; obesity ; Obesity - genetics ; patients ; phenotype ; polycystic ovary syndrome ; Polycystic Ovary Syndrome - genetics ; Polymorphism, Genetic ; regression analysis ; testosterone ; women</subject><ispartof>Gene, 2012-04, Vol.497 (1), p.38-44</ispartof><rights>2012 Elsevier B.V.</rights><rights>Copyright © 2012 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c379t-7c1f938772c9c2c6d90781d97d97b4115edbdac5ec2a843f68127479da832f2a3</citedby><cites>FETCH-LOGICAL-c379t-7c1f938772c9c2c6d90781d97d97b4115edbdac5ec2a843f68127479da832f2a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22306327$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Martínez-García, M.A.</creatorcontrib><creatorcontrib>San-Millán, J.L.</creatorcontrib><creatorcontrib>Escobar-Morreale, H.F.</creatorcontrib><title>The R453Q and D151A polymorphisms of Hexose-6-Phosphate Dehydrogenase Gene (H6PD) influence the polycystic ovary syndrome (PCOS) and obesity</title><title>Gene</title><addtitle>Gene</addtitle><description>Hexose-6-phosphate dehydrogenase (H6PDH) influences 11β-hydroxysteroid dehydrogenase activity, a key enzyme in the peripheral metabolism of cortisol that modulates insulin sensitivity in adipose tissue. To study the associations of R453Q and D151A polymorphisms in the H6PDH gene (H6PD) with polycystic ovary syndrome (PCOS) and their influence on clinical and metabolic variables, we genotyped 237 patients with PCOS and 135 control women for the R453Q (rs6688832) and D151A (rs34603401) variants in H6PD. The R453Q genotypes were distributed differently in patients and controls (χ2=9.55, P=0.002). Genotypes of D151A were distributed evenly in women with PCOS and controls, but showed a different distribution in non-obese and obese women (χ2=3.95, P=0.047), especially within the PCOS subgroup (χ2=4.65, P=0.031). A backward stepwise likelihood ratio logistic regression model (Nagelkerke's R2=0.490; χ2=164; P<0.0001) retained free testosterone (OR=1.13; 95% CI: 1.10–1.17) and H6PD Q453 alleles (OR=0.46; 95% CI: 0.27–0.79) as statistically significant predictors for PCOS, whereas homeostasis model assessment of insulin resistance and the H6PD D151A variant were excluded by the model. Both H6PD variants were associated with several phenotypic variables, including fasting insulin, homeostasis model assessment of insulin resistance and androstenedione levels. In summary, the R453Q and D151A variants of the H6PD gene are associated with PCOS and obesity, respectively, and may contribute to the PCOS phenotype by influencing obesity, insulin resistance and hyperandrogenism.
► Hexose-6-phosphate dehydrogenase influences peripheral cortisol metabolism. ► Hexose-6-phosphate dehydrogenase is encoded by H6PD. ► Q alleles of the R453Q variant in H6PD protect against PCOS. ► A alleles of the D151A variant in H6PD are associated with obesity. ► H6PD R453Q and D151A variants influence insulin resistance and hyperandrogenism.</description><subject>adipose tissue</subject><subject>Adrenal androgens</subject><subject>Adult</subject><subject>alleles</subject><subject>Androgen excess</subject><subject>androstenedione</subject><subject>animal ovaries</subject><subject>Carbohydrate Dehydrogenases - genetics</subject><subject>cortisol</subject><subject>fasting</subject><subject>Female</subject><subject>Genotype</subject><subject>homeostasis</subject><subject>Humans</subject><subject>hyperandrogenism</subject><subject>Hyperandrogenism - genetics</subject><subject>insulin</subject><subject>Insulin resistance</subject><subject>Insulin Resistance - genetics</subject><subject>Metabolism</subject><subject>obesity</subject><subject>Obesity - genetics</subject><subject>patients</subject><subject>phenotype</subject><subject>polycystic ovary syndrome</subject><subject>Polycystic Ovary Syndrome - genetics</subject><subject>Polymorphism, Genetic</subject><subject>regression analysis</subject><subject>testosterone</subject><subject>women</subject><issn>0378-1119</issn><issn>1879-0038</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNp9kc1u1DAUhS0EotPCC7AA76CLBP8kcSyxqWagg1SpA23Xlse-aTyaxKmdqcg79KFxmMISy5I33zm-9xyE3lGSU0Krz7v8HnrIGaEsJzQnhXiBFrQWMiOE1y_RgnBRZ5RSeYJOY9yRdMqSvUYnjHFScSYW6Om2BfyzKPkPrHuLV7SkF3jw-6nzYWhd7CL2DV7DLx8hq7JN6-PQ6hHwCtrJBp8m0BHwZRoEf1pXm9U5dn2zP0BvAI_Je_YyUxydwf5RhwnHqU-6LuGb5fXN-Z9v_RaiG6c36FWj9xHePr9n6O7b19vlOru6vvy-vLjKDBdyzIShjeS1EMxIw0xlJRE1tVKkuy0oLcFurTYlGKbrgjdVTZkohLS65qxhmp-hj0ffIfiHA8RRdS4a2O91D_4QlWRVVZSV5IlkR9IEH2OARg3BdWkNRYmaS1A7NZeg5hIUoSqVkETvn-0P2w7sP8nf1BPw4Qg02it9H1xUdzfJoUwFcSHKmfhyJCDF8OggqGjcnKl1AcyorHf_m-A34oCgQg</recordid><startdate>20120410</startdate><enddate>20120410</enddate><creator>Martínez-García, M.A.</creator><creator>San-Millán, J.L.</creator><creator>Escobar-Morreale, H.F.</creator><general>Elsevier B.V</general><scope>FBQ</scope><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>7X8</scope></search><sort><creationdate>20120410</creationdate><title>The R453Q and D151A polymorphisms of Hexose-6-Phosphate Dehydrogenase Gene (H6PD) influence the polycystic ovary syndrome (PCOS) and obesity</title><author>Martínez-García, M.A. ; San-Millán, J.L. ; Escobar-Morreale, H.F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c379t-7c1f938772c9c2c6d90781d97d97b4115edbdac5ec2a843f68127479da832f2a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>adipose tissue</topic><topic>Adrenal androgens</topic><topic>Adult</topic><topic>alleles</topic><topic>Androgen excess</topic><topic>androstenedione</topic><topic>animal ovaries</topic><topic>Carbohydrate Dehydrogenases - genetics</topic><topic>cortisol</topic><topic>fasting</topic><topic>Female</topic><topic>Genotype</topic><topic>homeostasis</topic><topic>Humans</topic><topic>hyperandrogenism</topic><topic>Hyperandrogenism - genetics</topic><topic>insulin</topic><topic>Insulin resistance</topic><topic>Insulin Resistance - genetics</topic><topic>Metabolism</topic><topic>obesity</topic><topic>Obesity - genetics</topic><topic>patients</topic><topic>phenotype</topic><topic>polycystic ovary syndrome</topic><topic>Polycystic Ovary Syndrome - genetics</topic><topic>Polymorphism, Genetic</topic><topic>regression analysis</topic><topic>testosterone</topic><topic>women</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Martínez-García, M.A.</creatorcontrib><creatorcontrib>San-Millán, J.L.</creatorcontrib><creatorcontrib>Escobar-Morreale, H.F.</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Gene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Martínez-García, M.A.</au><au>San-Millán, J.L.</au><au>Escobar-Morreale, H.F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The R453Q and D151A polymorphisms of Hexose-6-Phosphate Dehydrogenase Gene (H6PD) influence the polycystic ovary syndrome (PCOS) and obesity</atitle><jtitle>Gene</jtitle><addtitle>Gene</addtitle><date>2012-04-10</date><risdate>2012</risdate><volume>497</volume><issue>1</issue><spage>38</spage><epage>44</epage><pages>38-44</pages><issn>0378-1119</issn><eissn>1879-0038</eissn><abstract>Hexose-6-phosphate dehydrogenase (H6PDH) influences 11β-hydroxysteroid dehydrogenase activity, a key enzyme in the peripheral metabolism of cortisol that modulates insulin sensitivity in adipose tissue. To study the associations of R453Q and D151A polymorphisms in the H6PDH gene (H6PD) with polycystic ovary syndrome (PCOS) and their influence on clinical and metabolic variables, we genotyped 237 patients with PCOS and 135 control women for the R453Q (rs6688832) and D151A (rs34603401) variants in H6PD. The R453Q genotypes were distributed differently in patients and controls (χ2=9.55, P=0.002). Genotypes of D151A were distributed evenly in women with PCOS and controls, but showed a different distribution in non-obese and obese women (χ2=3.95, P=0.047), especially within the PCOS subgroup (χ2=4.65, P=0.031). A backward stepwise likelihood ratio logistic regression model (Nagelkerke's R2=0.490; χ2=164; P<0.0001) retained free testosterone (OR=1.13; 95% CI: 1.10–1.17) and H6PD Q453 alleles (OR=0.46; 95% CI: 0.27–0.79) as statistically significant predictors for PCOS, whereas homeostasis model assessment of insulin resistance and the H6PD D151A variant were excluded by the model. Both H6PD variants were associated with several phenotypic variables, including fasting insulin, homeostasis model assessment of insulin resistance and androstenedione levels. In summary, the R453Q and D151A variants of the H6PD gene are associated with PCOS and obesity, respectively, and may contribute to the PCOS phenotype by influencing obesity, insulin resistance and hyperandrogenism.
► Hexose-6-phosphate dehydrogenase influences peripheral cortisol metabolism. ► Hexose-6-phosphate dehydrogenase is encoded by H6PD. ► Q alleles of the R453Q variant in H6PD protect against PCOS. ► A alleles of the D151A variant in H6PD are associated with obesity. ► H6PD R453Q and D151A variants influence insulin resistance and hyperandrogenism.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>22306327</pmid><doi>10.1016/j.gene.2012.01.047</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0378-1119 |
| ispartof | Gene, 2012-04, Vol.497 (1), p.38-44 |
| issn | 0378-1119 1879-0038 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_926645693 |
| source | Elsevier:Jisc Collections:Elsevier Read and Publish Agreement 2022-2024:Freedom Collection (Reading list) |
| subjects | adipose tissue Adrenal androgens Adult alleles Androgen excess androstenedione animal ovaries Carbohydrate Dehydrogenases - genetics cortisol fasting Female Genotype homeostasis Humans hyperandrogenism Hyperandrogenism - genetics insulin Insulin resistance Insulin Resistance - genetics Metabolism obesity Obesity - genetics patients phenotype polycystic ovary syndrome Polycystic Ovary Syndrome - genetics Polymorphism, Genetic regression analysis testosterone women |
| title | The R453Q and D151A polymorphisms of Hexose-6-Phosphate Dehydrogenase Gene (H6PD) influence the polycystic ovary syndrome (PCOS) and obesity |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T02%3A35%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20R453Q%20and%20D151A%20polymorphisms%20of%20Hexose-6-Phosphate%20Dehydrogenase%20Gene%20(H6PD)%20influence%20the%20polycystic%20ovary%20syndrome%20(PCOS)%20and%20obesity&rft.jtitle=Gene&rft.au=Mart%C3%ADnez-Garc%C3%ADa,%20M.A.&rft.date=2012-04-10&rft.volume=497&rft.issue=1&rft.spage=38&rft.epage=44&rft.pages=38-44&rft.issn=0378-1119&rft.eissn=1879-0038&rft_id=info:doi/10.1016/j.gene.2012.01.047&rft_dat=%3Cproquest_cross%3E926645693%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c379t-7c1f938772c9c2c6d90781d97d97b4115edbdac5ec2a843f68127479da832f2a3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=926645693&rft_id=info:pmid/22306327&rfr_iscdi=true |