Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians
Adiponectin (ACRP30), an adipocyte-secreted protein encoded by the APM1 gene, is known to modulate insulin sensitivity and glucose homeostasis, those effects protecting obese mice from diabetes. Plasma adiponectin levels correlate well with insulin sensitivity in humans, and are decreased in both ty...
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| Veröffentlicht in: | Human molecular genetics 2002-10, Vol.11 (21), p.2607-2614 |
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| creator | Vasseur, Francis Helbecque, Nicole Dina, Christian Lobbens, Stéphane Delannoy, Valérie Gaget, Stéphane Boutin, Philippe Vaxillaire, Martine Leprêtre, Frédéric Dupont, Sophie Hara, Kazuo Clément, Karine Bihain, Bernard Kadowaki, Takashi Froguel, Philippe |
| description | Adiponectin (ACRP30), an adipocyte-secreted protein encoded by the APM1 gene, is known to modulate insulin sensitivity and glucose homeostasis, those effects protecting obese mice from diabetes. Plasma adiponectin levels correlate well with insulin sensitivity in humans, and are decreased in both type 2 diabetes (T2D) and obesity. We screened for single-nucleotide polymorphisms (SNPs) the APM1 gene coding and 5′ sequences in 40 French Caucasians: 12 SNPs and 4 rare non-synonymous mutations of exon 3 were detected. The 10 most frequent SNPs were genotyped in 1373 T2D and obese French Caucasian subjects and in all subjects available from 148 T2D multiplex families. The screening for rare mutations of exon 3 was extended to 1246 T2D and obese French subjects and to the members of the 148 T2D multiplex families. A haplotype including SNPs −11391 and −11377, both located in the 5′ sequences, was associated with adiponectin levels (P |
| doi_str_mv | 10.1093/hmg/11.21.2607 |
| format | Article |
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Plasma adiponectin levels correlate well with insulin sensitivity in humans, and are decreased in both type 2 diabetes (T2D) and obesity. We screened for single-nucleotide polymorphisms (SNPs) the APM1 gene coding and 5′ sequences in 40 French Caucasians: 12 SNPs and 4 rare non-synonymous mutations of exon 3 were detected. The 10 most frequent SNPs were genotyped in 1373 T2D and obese French Caucasian subjects and in all subjects available from 148 T2D multiplex families. The screening for rare mutations of exon 3 was extended to 1246 T2D and obese French subjects and to the members of the 148 T2D multiplex families. A haplotype including SNPs −11391 and −11377, both located in the 5′ sequences, was associated with adiponectin levels (P<0.0001) and with T2D (P=0.004). The presence of at least one non-synonymous mutation in exon 3 showed evidence of association with adiponectin levels (P=0.0009) and with T2D (P=0.005). We failed to detect an association with insulin resistance indexes. Although family-based association analysis with T2D did not reach significance, our results suggest that an at-risk haplotype of common variants located in the promoter and rare mutations in exon 3 contribute to the variation of the adipocyte-secreted adiponectin hormone level, and may be part of the genetic determinants for T2D in the French Caucasian population.</description><identifier>ISSN: 0964-6906</identifier><identifier>ISSN: 1460-2083</identifier><identifier>EISSN: 1460-2083</identifier><identifier>DOI: 10.1093/hmg/11.21.2607</identifier><identifier>PMID: 12354786</identifier><identifier>CODEN: HNGEE5</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Adipocytes ; Adipocytes - metabolism ; Adiponectin ; Biological and medical sciences ; Diabetes Mellitus, Type 2 ; Diabetes Mellitus, Type 2 - genetics ; Endocrinopathies ; Errors of metabolism ; European Continental Ancestry Group ; Exons ; France ; General aspects. Associated endocrine diseases. Endocrine paraneoplasic syndromes ; Genetic Predisposition to Disease ; Genetics ; Haplotypes ; Human genetics ; Humans ; Intercellular Signaling Peptides and Proteins ; Life Sciences ; Medical sciences ; Metabolic diseases ; Miscellaneous hereditary metabolic disorders ; Polymorphism, Single Nucleotide ; Promoter Regions (Genetics) ; Promoter Regions, Genetic ; Proteins ; Proteins - genetics ; Proteins - metabolism ; Whites - genetics</subject><ispartof>Human molecular genetics, 2002-10, Vol.11 (21), p.2607-2614</ispartof><rights>2002 INIST-CNRS</rights><rights>Copyright Oxford University Press(England) Oct 2, 2002</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c559t-89cc412aa3c52eff38104e004dcdd3b6c61b4dc5d01750aac42d25b126b7204b3</citedby><orcidid>0000-0002-2489-3355 ; 0000-0002-7722-7348 ; 0000-0003-4619-6785</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13934232$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12354786$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00174613$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Vasseur, Francis</creatorcontrib><creatorcontrib>Helbecque, Nicole</creatorcontrib><creatorcontrib>Dina, Christian</creatorcontrib><creatorcontrib>Lobbens, Stéphane</creatorcontrib><creatorcontrib>Delannoy, Valérie</creatorcontrib><creatorcontrib>Gaget, Stéphane</creatorcontrib><creatorcontrib>Boutin, Philippe</creatorcontrib><creatorcontrib>Vaxillaire, Martine</creatorcontrib><creatorcontrib>Leprêtre, Frédéric</creatorcontrib><creatorcontrib>Dupont, Sophie</creatorcontrib><creatorcontrib>Hara, Kazuo</creatorcontrib><creatorcontrib>Clément, Karine</creatorcontrib><creatorcontrib>Bihain, Bernard</creatorcontrib><creatorcontrib>Kadowaki, Takashi</creatorcontrib><creatorcontrib>Froguel, Philippe</creatorcontrib><title>Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians</title><title>Human molecular genetics</title><addtitle>Hum. Mol. Genet</addtitle><description>Adiponectin (ACRP30), an adipocyte-secreted protein encoded by the APM1 gene, is known to modulate insulin sensitivity and glucose homeostasis, those effects protecting obese mice from diabetes. Plasma adiponectin levels correlate well with insulin sensitivity in humans, and are decreased in both type 2 diabetes (T2D) and obesity. We screened for single-nucleotide polymorphisms (SNPs) the APM1 gene coding and 5′ sequences in 40 French Caucasians: 12 SNPs and 4 rare non-synonymous mutations of exon 3 were detected. The 10 most frequent SNPs were genotyped in 1373 T2D and obese French Caucasian subjects and in all subjects available from 148 T2D multiplex families. The screening for rare mutations of exon 3 was extended to 1246 T2D and obese French subjects and to the members of the 148 T2D multiplex families. A haplotype including SNPs −11391 and −11377, both located in the 5′ sequences, was associated with adiponectin levels (P<0.0001) and with T2D (P=0.004). The presence of at least one non-synonymous mutation in exon 3 showed evidence of association with adiponectin levels (P=0.0009) and with T2D (P=0.005). We failed to detect an association with insulin resistance indexes. Although family-based association analysis with T2D did not reach significance, our results suggest that an at-risk haplotype of common variants located in the promoter and rare mutations in exon 3 contribute to the variation of the adipocyte-secreted adiponectin hormone level, and may be part of the genetic determinants for T2D in the French Caucasian population.</description><subject>Adipocytes</subject><subject>Adipocytes - metabolism</subject><subject>Adiponectin</subject><subject>Biological and medical sciences</subject><subject>Diabetes Mellitus, Type 2</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Endocrinopathies</subject><subject>Errors of metabolism</subject><subject>European Continental Ancestry Group</subject><subject>Exons</subject><subject>France</subject><subject>General aspects. Associated endocrine diseases. Endocrine paraneoplasic syndromes</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetics</subject><subject>Haplotypes</subject><subject>Human genetics</subject><subject>Humans</subject><subject>Intercellular Signaling Peptides and Proteins</subject><subject>Life Sciences</subject><subject>Medical sciences</subject><subject>Metabolic diseases</subject><subject>Miscellaneous hereditary metabolic disorders</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Promoter Regions (Genetics)</subject><subject>Promoter Regions, Genetic</subject><subject>Proteins</subject><subject>Proteins - genetics</subject><subject>Proteins - metabolism</subject><subject>Whites - genetics</subject><issn>0964-6906</issn><issn>1460-2083</issn><issn>1460-2083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks9rFDEUgAdRbK1ePUoQFDxMmx8zmZ3jurVWXFGoivQSMpk3nbSZZEwypfsP-3eY2V1a8CIE8nj53sdL8rLsJcHHBNfspB-uTgg5pmlxXD3KDknBcU7xgj3ODnHNi5zXmB9kz0K4xpjwglVPswNCWVlUC36Y_bnQ9spAbidlwEXdAhqd2QzOj70OA-rlaFzcjBCQtij2gBoXezR6d6cHaeZgcBE8krZFcOcsYsh1W3D57QtBV2ABDa6djIyAZKtHpzYR8gDKQ4R2l7KgYtL3zg8pRgZuwYStUjkbvW6mVBzdVjsbo1bI63CDOufR3B2iqNWyScZtn2cerOrRSk5KBi1teJ496aQJ8GK_H2U_zj58X53n668fP62W61yVZR3zRa1UQaiUTJUUuo4tCC4A46JVbcsarjhpUly2mFQlllIVtKVlQyhvKoqLhh1l73beXhox-vREfiOc1OJ8uRZzLv1BVXDCbkli3-7Y9Ia_JwhRDDooMEZacFMQFSWM8gr_FySLslgQOhtf_wNeu8nbdGFBCWG4KuoqQcc7SHkXgofuvk-CxTxTIs2UICSViHmmUsGrvXVqBmgf8P0QJeDNHpBBSdN5aZUODxyrWUEZTVy-43SIcHd_Lv2N4BWrSnH-61L8fH96erH6vBaX7C9lAOfC</recordid><startdate>20021001</startdate><enddate>20021001</enddate><creator>Vasseur, Francis</creator><creator>Helbecque, Nicole</creator><creator>Dina, Christian</creator><creator>Lobbens, Stéphane</creator><creator>Delannoy, Valérie</creator><creator>Gaget, Stéphane</creator><creator>Boutin, Philippe</creator><creator>Vaxillaire, Martine</creator><creator>Leprêtre, Frédéric</creator><creator>Dupont, Sophie</creator><creator>Hara, Kazuo</creator><creator>Clément, Karine</creator><creator>Bihain, Bernard</creator><creator>Kadowaki, Takashi</creator><creator>Froguel, Philippe</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><general>Oxford University Press (OUP)</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>7QP</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-2489-3355</orcidid><orcidid>https://orcid.org/0000-0002-7722-7348</orcidid><orcidid>https://orcid.org/0000-0003-4619-6785</orcidid></search><sort><creationdate>20021001</creationdate><title>Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians</title><author>Vasseur, Francis ; Helbecque, Nicole ; Dina, Christian ; Lobbens, Stéphane ; Delannoy, Valérie ; Gaget, Stéphane ; Boutin, Philippe ; Vaxillaire, Martine ; Leprêtre, Frédéric ; Dupont, Sophie ; Hara, Kazuo ; Clément, Karine ; Bihain, Bernard ; Kadowaki, Takashi ; Froguel, Philippe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c559t-89cc412aa3c52eff38104e004dcdd3b6c61b4dc5d01750aac42d25b126b7204b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adipocytes</topic><topic>Adipocytes - metabolism</topic><topic>Adiponectin</topic><topic>Biological and medical sciences</topic><topic>Diabetes Mellitus, Type 2</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Endocrinopathies</topic><topic>Errors of metabolism</topic><topic>European Continental Ancestry Group</topic><topic>Exons</topic><topic>France</topic><topic>General aspects. Associated endocrine diseases. Endocrine paraneoplasic syndromes</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetics</topic><topic>Haplotypes</topic><topic>Human genetics</topic><topic>Humans</topic><topic>Intercellular Signaling Peptides and Proteins</topic><topic>Life Sciences</topic><topic>Medical sciences</topic><topic>Metabolic diseases</topic><topic>Miscellaneous hereditary metabolic disorders</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Promoter Regions (Genetics)</topic><topic>Promoter Regions, Genetic</topic><topic>Proteins</topic><topic>Proteins - genetics</topic><topic>Proteins - metabolism</topic><topic>Whites - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vasseur, Francis</creatorcontrib><creatorcontrib>Helbecque, Nicole</creatorcontrib><creatorcontrib>Dina, Christian</creatorcontrib><creatorcontrib>Lobbens, Stéphane</creatorcontrib><creatorcontrib>Delannoy, Valérie</creatorcontrib><creatorcontrib>Gaget, Stéphane</creatorcontrib><creatorcontrib>Boutin, Philippe</creatorcontrib><creatorcontrib>Vaxillaire, Martine</creatorcontrib><creatorcontrib>Leprêtre, Frédéric</creatorcontrib><creatorcontrib>Dupont, Sophie</creatorcontrib><creatorcontrib>Hara, Kazuo</creatorcontrib><creatorcontrib>Clément, Karine</creatorcontrib><creatorcontrib>Bihain, Bernard</creatorcontrib><creatorcontrib>Kadowaki, Takashi</creatorcontrib><creatorcontrib>Froguel, Philippe</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>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Human molecular genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vasseur, Francis</au><au>Helbecque, Nicole</au><au>Dina, Christian</au><au>Lobbens, Stéphane</au><au>Delannoy, Valérie</au><au>Gaget, Stéphane</au><au>Boutin, Philippe</au><au>Vaxillaire, Martine</au><au>Leprêtre, Frédéric</au><au>Dupont, Sophie</au><au>Hara, Kazuo</au><au>Clément, Karine</au><au>Bihain, Bernard</au><au>Kadowaki, Takashi</au><au>Froguel, Philippe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians</atitle><jtitle>Human molecular genetics</jtitle><addtitle>Hum. Mol. Genet</addtitle><date>2002-10-01</date><risdate>2002</risdate><volume>11</volume><issue>21</issue><spage>2607</spage><epage>2614</epage><pages>2607-2614</pages><issn>0964-6906</issn><issn>1460-2083</issn><eissn>1460-2083</eissn><coden>HNGEE5</coden><abstract>Adiponectin (ACRP30), an adipocyte-secreted protein encoded by the APM1 gene, is known to modulate insulin sensitivity and glucose homeostasis, those effects protecting obese mice from diabetes. Plasma adiponectin levels correlate well with insulin sensitivity in humans, and are decreased in both type 2 diabetes (T2D) and obesity. We screened for single-nucleotide polymorphisms (SNPs) the APM1 gene coding and 5′ sequences in 40 French Caucasians: 12 SNPs and 4 rare non-synonymous mutations of exon 3 were detected. The 10 most frequent SNPs were genotyped in 1373 T2D and obese French Caucasian subjects and in all subjects available from 148 T2D multiplex families. The screening for rare mutations of exon 3 was extended to 1246 T2D and obese French subjects and to the members of the 148 T2D multiplex families. A haplotype including SNPs −11391 and −11377, both located in the 5′ sequences, was associated with adiponectin levels (P<0.0001) and with T2D (P=0.004). The presence of at least one non-synonymous mutation in exon 3 showed evidence of association with adiponectin levels (P=0.0009) and with T2D (P=0.005). We failed to detect an association with insulin resistance indexes. Although family-based association analysis with T2D did not reach significance, our results suggest that an at-risk haplotype of common variants located in the promoter and rare mutations in exon 3 contribute to the variation of the adipocyte-secreted adiponectin hormone level, and may be part of the genetic determinants for T2D in the French Caucasian population.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>12354786</pmid><doi>10.1093/hmg/11.21.2607</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-2489-3355</orcidid><orcidid>https://orcid.org/0000-0002-7722-7348</orcidid><orcidid>https://orcid.org/0000-0003-4619-6785</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adipocytes Adipocytes - metabolism Adiponectin Biological and medical sciences Diabetes Mellitus, Type 2 Diabetes Mellitus, Type 2 - genetics Endocrinopathies Errors of metabolism European Continental Ancestry Group Exons France General aspects. Associated endocrine diseases. Endocrine paraneoplasic syndromes Genetic Predisposition to Disease Genetics Haplotypes Human genetics Humans Intercellular Signaling Peptides and Proteins Life Sciences Medical sciences Metabolic diseases Miscellaneous hereditary metabolic disorders Polymorphism, Single Nucleotide Promoter Regions (Genetics) Promoter Regions, Genetic Proteins Proteins - genetics Proteins - metabolism Whites - genetics |
| title | Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians |
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