Aryl hydrocarbon receptor nuclear translocator (ARNT) gene as a positional and functional candidate for type 2 diabetes and prediabetic intermediate traits: Mutation detection, case-control studies, and gene expression analysis
<p>Abstract</p> <p>Background</p> <p>ARNT, a member of the basic helix-loop-helix family of transcription factors, is located on human chromosome 1q21–q24, a region which showed well replicated linkage to type 2 diabetes. We hypothesized that common polymorphisms in the...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2008-03-01
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| Series: | BMC Medical Genetics |
| Online Access: | http://www.biomedcentral.com/1471-2350/9/16 |
| _version_ | 1818908918389145600 |
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| author | Chu Winston S Sharma Neeraj K Das Swapan K Wang Hua Elbein Steven C |
| author_facet | Chu Winston S Sharma Neeraj K Das Swapan K Wang Hua Elbein Steven C |
| author_sort | Chu Winston S |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>ARNT, a member of the basic helix-loop-helix family of transcription factors, is located on human chromosome 1q21–q24, a region which showed well replicated linkage to type 2 diabetes. We hypothesized that common polymorphisms in the <it>ARNT </it>gene might increase the susceptibility to type 2 diabetes through impaired glucose-stimulated insulin secretion.</p> <p>Methods</p> <p>We selected 9 single nucleotide polymorphisms to tag common variation across the <it>ARNT </it>gene. Additionally we searched for novel variants in functional coding domains in European American and African American samples. Case-control studies were performed in 191 European American individuals with type 2 diabetes and 187 nondiabetic European American control individuals, and in 372 African American individuals with type 2 diabetes and 194 African American control individuals. Metabolic effects of <it>ARNT </it>variants were examined in 122 members of 26 European American families from Utah and in 225 unrelated individuals from Arkansas. Gene expression was tested in 8 sibling pairs discordant for type 2 diabetes.</p> <p>Results</p> <p>No nonsynonymous variants or novel polymorphisms were identified. No SNP was associated with type 2 diabetes in either African Americans or European Americans, but among nondiabetic European American individuals, <it>ARNT </it>SNPs rs188970 and rs11204735 were associated with acute insulin response (AIR<sub>g</sub>; p =< 0.005). SNP rs2134688 interacted with body mass index to alter β-cell compensation to insulin resistance (disposition index; p = 0.004). No significant difference in <it>ARNT </it>mRNA levels was observed in transformed lymphocytes from sibling pairs discordant for type 2 diabetes.</p> <p>Conclusion</p> <p>Common <it>ARNT </it>variants are unlikely to explain the linkage signal on chromosome 1q, but may alter insulin secretion in nondiabetic subjects. Our studies cannot exclude a role for rare variants or variants of small (< 1.6) effect size.</p> |
| first_indexed | 2024-12-19T22:18:39Z |
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| id | doaj.art-3793dd5b7f3f44d9ba3aff21f57d83dc |
| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-19T22:18:39Z |
| publishDate | 2008-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genetics |
| spelling | doaj.art-3793dd5b7f3f44d9ba3aff21f57d83dc2022-12-21T20:03:42ZengBMCBMC Medical Genetics1471-23502008-03-01911610.1186/1471-2350-9-16Aryl hydrocarbon receptor nuclear translocator (ARNT) gene as a positional and functional candidate for type 2 diabetes and prediabetic intermediate traits: Mutation detection, case-control studies, and gene expression analysisChu Winston SSharma Neeraj KDas Swapan KWang HuaElbein Steven C<p>Abstract</p> <p>Background</p> <p>ARNT, a member of the basic helix-loop-helix family of transcription factors, is located on human chromosome 1q21–q24, a region which showed well replicated linkage to type 2 diabetes. We hypothesized that common polymorphisms in the <it>ARNT </it>gene might increase the susceptibility to type 2 diabetes through impaired glucose-stimulated insulin secretion.</p> <p>Methods</p> <p>We selected 9 single nucleotide polymorphisms to tag common variation across the <it>ARNT </it>gene. Additionally we searched for novel variants in functional coding domains in European American and African American samples. Case-control studies were performed in 191 European American individuals with type 2 diabetes and 187 nondiabetic European American control individuals, and in 372 African American individuals with type 2 diabetes and 194 African American control individuals. Metabolic effects of <it>ARNT </it>variants were examined in 122 members of 26 European American families from Utah and in 225 unrelated individuals from Arkansas. Gene expression was tested in 8 sibling pairs discordant for type 2 diabetes.</p> <p>Results</p> <p>No nonsynonymous variants or novel polymorphisms were identified. No SNP was associated with type 2 diabetes in either African Americans or European Americans, but among nondiabetic European American individuals, <it>ARNT </it>SNPs rs188970 and rs11204735 were associated with acute insulin response (AIR<sub>g</sub>; p =< 0.005). SNP rs2134688 interacted with body mass index to alter β-cell compensation to insulin resistance (disposition index; p = 0.004). No significant difference in <it>ARNT </it>mRNA levels was observed in transformed lymphocytes from sibling pairs discordant for type 2 diabetes.</p> <p>Conclusion</p> <p>Common <it>ARNT </it>variants are unlikely to explain the linkage signal on chromosome 1q, but may alter insulin secretion in nondiabetic subjects. Our studies cannot exclude a role for rare variants or variants of small (< 1.6) effect size.</p>http://www.biomedcentral.com/1471-2350/9/16 |
| spellingShingle | Chu Winston S Sharma Neeraj K Das Swapan K Wang Hua Elbein Steven C Aryl hydrocarbon receptor nuclear translocator (ARNT) gene as a positional and functional candidate for type 2 diabetes and prediabetic intermediate traits: Mutation detection, case-control studies, and gene expression analysis BMC Medical Genetics |
| title | Aryl hydrocarbon receptor nuclear translocator (ARNT) gene as a positional and functional candidate for type 2 diabetes and prediabetic intermediate traits: Mutation detection, case-control studies, and gene expression analysis |
| title_full | Aryl hydrocarbon receptor nuclear translocator (ARNT) gene as a positional and functional candidate for type 2 diabetes and prediabetic intermediate traits: Mutation detection, case-control studies, and gene expression analysis |
| title_fullStr | Aryl hydrocarbon receptor nuclear translocator (ARNT) gene as a positional and functional candidate for type 2 diabetes and prediabetic intermediate traits: Mutation detection, case-control studies, and gene expression analysis |
| title_full_unstemmed | Aryl hydrocarbon receptor nuclear translocator (ARNT) gene as a positional and functional candidate for type 2 diabetes and prediabetic intermediate traits: Mutation detection, case-control studies, and gene expression analysis |
| title_short | Aryl hydrocarbon receptor nuclear translocator (ARNT) gene as a positional and functional candidate for type 2 diabetes and prediabetic intermediate traits: Mutation detection, case-control studies, and gene expression analysis |
| title_sort | aryl hydrocarbon receptor nuclear translocator arnt gene as a positional and functional candidate for type 2 diabetes and prediabetic intermediate traits mutation detection case control studies and gene expression analysis |
| url | http://www.biomedcentral.com/1471-2350/9/16 |
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