DGAT1 promoter polymorphism associated with alterations in body mass index, high density lipoprotein levels and blood pressure in Turkish women
Triglyceride synthesis is catalyzed by acyl CoA:diacylglycerol acyltransferases (DGAT), microsomal enzymes that use diacylglycerol and fatty acyl CoAs as substrates. Because DGAT1 expression is up‐regulated during adipocyte differentiation and DGAT1 deficiency is associated with leanness in mice, we...
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| Veröffentlicht in: | Clinical genetics 2002-07, Vol.62 (1), p.68-73 |
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| creator | Ludwig, EH Mahley, RW Palaoglu, E Özbayrakçı, S Balestra, ME Borecki, IB Innerarity, TL Farese Jr, RV |
| description | Triglyceride synthesis is catalyzed by acyl CoA:diacylglycerol acyltransferases (DGAT), microsomal enzymes that use diacylglycerol and fatty acyl CoAs as substrates. Because DGAT1 expression is up‐regulated during adipocyte differentiation and DGAT1 deficiency is associated with leanness in mice, we hypothesized that alterations in DGAT1 expression may affect human body weight. We identified five polymorphisms in the human DGAT1 promoter and 5′ non‐coding sequence in a random Turkish population. Functional analysis of one common variant, C79T, revealed reduced promoter activity for the 79T allele in cultured cell lines. In 476 Turkish women, the 79T allele was associated with lower body mass index (BMI) (p = 0.004), conferring an odds ratio of 2.0 (95% CI = 1.30–3.07, p = 0.0001) for BMI ≤ 20. Interestingly, after controlling for the influence of BMI, the 79T allele was also associated with higher plasma HDL cholesterol levels (p = 0.0006) and lower diastolic blood pressure (p = 0.019) in these women. No association was found in Turkish men (n = 846). Our findings suggest that genetic variation at the DGAT1 locus may influence BMI and other metabolic parameters associated with cardiovascular risk in selected human populations. |
| doi_str_mv | 10.1034/j.1399-0004.2002.620109.x |
| format | Article |
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Because DGAT1 expression is up‐regulated during adipocyte differentiation and DGAT1 deficiency is associated with leanness in mice, we hypothesized that alterations in DGAT1 expression may affect human body weight. We identified five polymorphisms in the human DGAT1 promoter and 5′ non‐coding sequence in a random Turkish population. Functional analysis of one common variant, C79T, revealed reduced promoter activity for the 79T allele in cultured cell lines. In 476 Turkish women, the 79T allele was associated with lower body mass index (BMI) (p = 0.004), conferring an odds ratio of 2.0 (95% CI = 1.30–3.07, p = 0.0001) for BMI ≤ 20. Interestingly, after controlling for the influence of BMI, the 79T allele was also associated with higher plasma HDL cholesterol levels (p = 0.0006) and lower diastolic blood pressure (p = 0.019) in these women. No association was found in Turkish men (n = 846). Our findings suggest that genetic variation at the DGAT1 locus may influence BMI and other metabolic parameters associated with cardiovascular risk in selected human populations.</description><identifier>ISSN: 0009-9163</identifier><identifier>EISSN: 1399-0004</identifier><identifier>DOI: 10.1034/j.1399-0004.2002.620109.x</identifier><identifier>PMID: 12123490</identifier><identifier>CODEN: CLGNAY</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science, Ltd</publisher><subject>acyl CoA:diacylglycerol acyltransferase ; Acyltransferases - genetics ; Adult ; Biological and medical sciences ; Body Mass Index ; Body Weight - genetics ; Cholesterol, HDL - blood ; Classical genetics, quantitative genetics, hybrids ; Diacylglycerol O-Acyltransferase ; Female ; Fundamental and applied biological sciences. Psychology ; genetic association ; Genetics of eukaryotes. Biological and molecular evolution ; Human ; Humans ; Male ; metabolic syndrome ; Polymorphism, Genetic ; Promoter Regions, Genetic ; single nucleotide polymorphism ; syndrome X ; triacylglycerol ; triglyceride ; Turkey</subject><ispartof>Clinical genetics, 2002-07, Vol.62 (1), p.68-73</ispartof><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4389-b7611e159b3df970a242c6a21f5fa48b72210cfa12ca0160c327986002c0dc433</citedby><cites>FETCH-LOGICAL-c4389-b7611e159b3df970a242c6a21f5fa48b72210cfa12ca0160c327986002c0dc433</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1034%2Fj.1399-0004.2002.620109.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1034%2Fj.1399-0004.2002.620109.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13797538$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12123490$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ludwig, EH</creatorcontrib><creatorcontrib>Mahley, RW</creatorcontrib><creatorcontrib>Palaoglu, E</creatorcontrib><creatorcontrib>Özbayrakçı, S</creatorcontrib><creatorcontrib>Balestra, ME</creatorcontrib><creatorcontrib>Borecki, IB</creatorcontrib><creatorcontrib>Innerarity, TL</creatorcontrib><creatorcontrib>Farese Jr, RV</creatorcontrib><title>DGAT1 promoter polymorphism associated with alterations in body mass index, high density lipoprotein levels and blood pressure in Turkish women</title><title>Clinical genetics</title><addtitle>Clin Genet</addtitle><description>Triglyceride synthesis is catalyzed by acyl CoA:diacylglycerol acyltransferases (DGAT), microsomal enzymes that use diacylglycerol and fatty acyl CoAs as substrates. Because DGAT1 expression is up‐regulated during adipocyte differentiation and DGAT1 deficiency is associated with leanness in mice, we hypothesized that alterations in DGAT1 expression may affect human body weight. We identified five polymorphisms in the human DGAT1 promoter and 5′ non‐coding sequence in a random Turkish population. Functional analysis of one common variant, C79T, revealed reduced promoter activity for the 79T allele in cultured cell lines. In 476 Turkish women, the 79T allele was associated with lower body mass index (BMI) (p = 0.004), conferring an odds ratio of 2.0 (95% CI = 1.30–3.07, p = 0.0001) for BMI ≤ 20. Interestingly, after controlling for the influence of BMI, the 79T allele was also associated with higher plasma HDL cholesterol levels (p = 0.0006) and lower diastolic blood pressure (p = 0.019) in these women. No association was found in Turkish men (n = 846). Our findings suggest that genetic variation at the DGAT1 locus may influence BMI and other metabolic parameters associated with cardiovascular risk in selected human populations.</description><subject>acyl CoA:diacylglycerol acyltransferase</subject><subject>Acyltransferases - genetics</subject><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Body Mass Index</subject><subject>Body Weight - genetics</subject><subject>Cholesterol, HDL - blood</subject><subject>Classical genetics, quantitative genetics, hybrids</subject><subject>Diacylglycerol O-Acyltransferase</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>genetic association</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Human</subject><subject>Humans</subject><subject>Male</subject><subject>metabolic syndrome</subject><subject>Polymorphism, Genetic</subject><subject>Promoter Regions, Genetic</subject><subject>single nucleotide polymorphism</subject><subject>syndrome X</subject><subject>triacylglycerol</subject><subject>triglyceride</subject><subject>Turkey</subject><issn>0009-9163</issn><issn>1399-0004</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks9u1DAQxi0EotvCKyBzgBMJ_pPE6xvV0gakCi6LerQcxyHeOnGwE3bzFH1lHGXVXjmNR_Obb0bfGID3GKUY0ezzIcWU8wQhlKUEIZIWBGHE09MLsHmqvASbGHjCcUEvwGUIh5hSlvPX4AITTGjG0QY8fi2v9xgO3nVu1B4Ozs6d80NrQgdlCE4ZOeoaHs3YQmkjIkfj-gBNDytXz7CLUExqffoEW_O7hbXugxlnaM3gouyoI2n1X20DlH0NK-tcHefpECavF5n95B9MaOHRdbp_A1410gb99hyvwK_bm_3uW3L3s_y-u75LVEa3PKlYgbHGOa9o3XCGJMmIKiTBTd7IbFsxQjBSjcRESYQLpChhfFtErxSqowS9Ah9X3bjin0mHUXQmKG2t7LWbgmCYExa9jCBfQeVdCF43YvCmk34WGInlGuIgFs_F4rlYriHWa4hT7H13HjJVna6fO8_2R-DDGZBBSdt42SsTnjnKOMvpNnJfVu5orJ7_fwOxK2_Wd5RIVgkTRn16kpD-QRQsfgtx_6MUtztW5hmh4p7-A8BItvU</recordid><startdate>200207</startdate><enddate>200207</enddate><creator>Ludwig, EH</creator><creator>Mahley, RW</creator><creator>Palaoglu, E</creator><creator>Özbayrakçı, S</creator><creator>Balestra, ME</creator><creator>Borecki, IB</creator><creator>Innerarity, TL</creator><creator>Farese Jr, RV</creator><general>Blackwell Science, Ltd</general><general>Blackwell</general><scope>BSCLL</scope><scope>IQODW</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>200207</creationdate><title>DGAT1 promoter polymorphism associated with alterations in body mass index, high density lipoprotein levels and blood pressure in Turkish women</title><author>Ludwig, EH ; Mahley, RW ; Palaoglu, E ; Özbayrakçı, S ; Balestra, ME ; Borecki, IB ; Innerarity, TL ; Farese Jr, RV</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4389-b7611e159b3df970a242c6a21f5fa48b72210cfa12ca0160c327986002c0dc433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>acyl CoA:diacylglycerol acyltransferase</topic><topic>Acyltransferases - genetics</topic><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Body Mass Index</topic><topic>Body Weight - genetics</topic><topic>Cholesterol, HDL - blood</topic><topic>Classical genetics, quantitative genetics, hybrids</topic><topic>Diacylglycerol O-Acyltransferase</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>genetic association</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Human</topic><topic>Humans</topic><topic>Male</topic><topic>metabolic syndrome</topic><topic>Polymorphism, Genetic</topic><topic>Promoter Regions, Genetic</topic><topic>single nucleotide polymorphism</topic><topic>syndrome X</topic><topic>triacylglycerol</topic><topic>triglyceride</topic><topic>Turkey</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ludwig, EH</creatorcontrib><creatorcontrib>Mahley, RW</creatorcontrib><creatorcontrib>Palaoglu, E</creatorcontrib><creatorcontrib>Özbayrakçı, S</creatorcontrib><creatorcontrib>Balestra, ME</creatorcontrib><creatorcontrib>Borecki, IB</creatorcontrib><creatorcontrib>Innerarity, TL</creatorcontrib><creatorcontrib>Farese Jr, RV</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</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>Clinical genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ludwig, EH</au><au>Mahley, RW</au><au>Palaoglu, E</au><au>Özbayrakçı, S</au><au>Balestra, ME</au><au>Borecki, IB</au><au>Innerarity, TL</au><au>Farese Jr, RV</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DGAT1 promoter polymorphism associated with alterations in body mass index, high density lipoprotein levels and blood pressure in Turkish women</atitle><jtitle>Clinical genetics</jtitle><addtitle>Clin Genet</addtitle><date>2002-07</date><risdate>2002</risdate><volume>62</volume><issue>1</issue><spage>68</spage><epage>73</epage><pages>68-73</pages><issn>0009-9163</issn><eissn>1399-0004</eissn><coden>CLGNAY</coden><abstract>Triglyceride synthesis is catalyzed by acyl CoA:diacylglycerol acyltransferases (DGAT), microsomal enzymes that use diacylglycerol and fatty acyl CoAs as substrates. Because DGAT1 expression is up‐regulated during adipocyte differentiation and DGAT1 deficiency is associated with leanness in mice, we hypothesized that alterations in DGAT1 expression may affect human body weight. We identified five polymorphisms in the human DGAT1 promoter and 5′ non‐coding sequence in a random Turkish population. Functional analysis of one common variant, C79T, revealed reduced promoter activity for the 79T allele in cultured cell lines. In 476 Turkish women, the 79T allele was associated with lower body mass index (BMI) (p = 0.004), conferring an odds ratio of 2.0 (95% CI = 1.30–3.07, p = 0.0001) for BMI ≤ 20. Interestingly, after controlling for the influence of BMI, the 79T allele was also associated with higher plasma HDL cholesterol levels (p = 0.0006) and lower diastolic blood pressure (p = 0.019) in these women. No association was found in Turkish men (n = 846). Our findings suggest that genetic variation at the DGAT1 locus may influence BMI and other metabolic parameters associated with cardiovascular risk in selected human populations.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science, Ltd</pub><pmid>12123490</pmid><doi>10.1034/j.1399-0004.2002.620109.x</doi><tpages>6</tpages></addata></record> |
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| ispartof | Clinical genetics, 2002-07, Vol.62 (1), p.68-73 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | acyl CoA:diacylglycerol acyltransferase Acyltransferases - genetics Adult Biological and medical sciences Body Mass Index Body Weight - genetics Cholesterol, HDL - blood Classical genetics, quantitative genetics, hybrids Diacylglycerol O-Acyltransferase Female Fundamental and applied biological sciences. Psychology genetic association Genetics of eukaryotes. Biological and molecular evolution Human Humans Male metabolic syndrome Polymorphism, Genetic Promoter Regions, Genetic single nucleotide polymorphism syndrome X triacylglycerol triglyceride Turkey |
| title | DGAT1 promoter polymorphism associated with alterations in body mass index, high density lipoprotein levels and blood pressure in Turkish women |
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