Lack of association of the <it>HMGA1</it> IVS5-13insC variant with type 2 diabetes in an ethnically diverse hypertensive case control cohort
<p>Abstract</p> <p>Background</p> <p>Recently, the high-mobility group A1 gene (<it>HMGA1</it>) variant IVS5-13insC has been associated with type 2 diabetes, but reported associations are inconsistent and data are lacking in Hispanic and African American pop...
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| Format: | Article |
| Language: | English |
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BMC
2013-01-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://www.translational-medicine.com/content/11/1/12 |
| _version_ | 1818514126685601792 |
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| author | Karnes Jason H Langaee Taimour Y McDonough Caitrin W Chang Shin-Wen Ramos Miguel Catlin Jr James R Casanova Octavio E Gong Yan Pepine Carl J Johnson Julie A Cooper-DeHoff Rhonda M |
| author_facet | Karnes Jason H Langaee Taimour Y McDonough Caitrin W Chang Shin-Wen Ramos Miguel Catlin Jr James R Casanova Octavio E Gong Yan Pepine Carl J Johnson Julie A Cooper-DeHoff Rhonda M |
| author_sort | Karnes Jason H |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Recently, the high-mobility group A1 gene (<it>HMGA1</it>) variant IVS5-13insC has been associated with type 2 diabetes, but reported associations are inconsistent and data are lacking in Hispanic and African American populations. We sought to investigate the <it>HMGA1</it>-diabetes association and to characterize IVS5-13insC allele frequencies and linkage disequilibrium (LD) in 3,070 Caucasian, Hispanic, and African American patients from the INternational VErapamil SR-Trandolapril STudy (INVEST).</p> <p>Methods</p> <p>INVEST was a randomized, multicenter trial comparing two antihypertensive treatment strategies in an ethnically diverse cohort of hypertensive, coronary artery disease patients. Controls, who were diabetes-free throughout the study, and type 2 diabetes cases, either prevalent or incident, were genotyped for IVS5-13insC using Taqman®, confirmed with Pyrosequencing and Sanger sequencing. For LD analysis, genotyping for eight additional <it>HMGA1</it> single nucleotide polymorphisms (SNPs) was performed using the Illumina® HumanCVD BeadChip. We used logistic regression to test association of the <it>HMGA1</it> IVS5-13insC and diabetes, adjusted for age, gender, body mass index, and percentage European, African, and Native American ancestry.</p> <p>Results</p> <p>We observed IVS5-13insC minor allele frequencies consistent with previous literature in Caucasians and African Americans (0.03 in cases and 0.04 in controls for both race/ethnic groups), and higher frequencies in Hispanics (0.07 in cases and 0.07 in controls). The IVS5-13insC was not associated with type 2 diabetes overall (odds ratio 0.98 [0.76-1.26], p=0.88) or in any race/ethnic group. Pairwise LD (r<sup>2</sup>) of IVS5-13insC and rs9394200, a SNP previously used as a tag SNP for IVS5-13insC, was low (r<sup>2</sup>=0.47 in Caucasians, r<sup>2</sup>=0.25 in Hispanics, and r<sup>2</sup>=0.06 in African Americans). Furthermore, <it>in silico</it> analysis suggested a lack of functional consequences for the IVS5-13insC variant.</p> <p>Conclusions</p> <p>Our results suggest that IVS5-13insC is not a functional variant and not associated with type 2 diabetes in an ethnically diverse, hypertensive, coronary artery disease population. Larger, more adequately powered studies need to be performed to confirm our findings.</p> <p>Trial registration</p> <p>clinicaltrials.gov (NCT00133692)</p> |
| first_indexed | 2024-12-11T00:11:26Z |
| format | Article |
| id | doaj.art-0d315941e342429d94814a6900c5d3f2 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-11T00:11:26Z |
| publishDate | 2013-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-0d315941e342429d94814a6900c5d3f22022-12-22T01:28:07ZengBMCJournal of Translational Medicine1479-58762013-01-011111210.1186/1479-5876-11-12Lack of association of the <it>HMGA1</it> IVS5-13insC variant with type 2 diabetes in an ethnically diverse hypertensive case control cohortKarnes Jason HLangaee Taimour YMcDonough Caitrin WChang Shin-WenRamos MiguelCatlin Jr James RCasanova Octavio EGong YanPepine Carl JJohnson Julie ACooper-DeHoff Rhonda M<p>Abstract</p> <p>Background</p> <p>Recently, the high-mobility group A1 gene (<it>HMGA1</it>) variant IVS5-13insC has been associated with type 2 diabetes, but reported associations are inconsistent and data are lacking in Hispanic and African American populations. We sought to investigate the <it>HMGA1</it>-diabetes association and to characterize IVS5-13insC allele frequencies and linkage disequilibrium (LD) in 3,070 Caucasian, Hispanic, and African American patients from the INternational VErapamil SR-Trandolapril STudy (INVEST).</p> <p>Methods</p> <p>INVEST was a randomized, multicenter trial comparing two antihypertensive treatment strategies in an ethnically diverse cohort of hypertensive, coronary artery disease patients. Controls, who were diabetes-free throughout the study, and type 2 diabetes cases, either prevalent or incident, were genotyped for IVS5-13insC using Taqman®, confirmed with Pyrosequencing and Sanger sequencing. For LD analysis, genotyping for eight additional <it>HMGA1</it> single nucleotide polymorphisms (SNPs) was performed using the Illumina® HumanCVD BeadChip. We used logistic regression to test association of the <it>HMGA1</it> IVS5-13insC and diabetes, adjusted for age, gender, body mass index, and percentage European, African, and Native American ancestry.</p> <p>Results</p> <p>We observed IVS5-13insC minor allele frequencies consistent with previous literature in Caucasians and African Americans (0.03 in cases and 0.04 in controls for both race/ethnic groups), and higher frequencies in Hispanics (0.07 in cases and 0.07 in controls). The IVS5-13insC was not associated with type 2 diabetes overall (odds ratio 0.98 [0.76-1.26], p=0.88) or in any race/ethnic group. Pairwise LD (r<sup>2</sup>) of IVS5-13insC and rs9394200, a SNP previously used as a tag SNP for IVS5-13insC, was low (r<sup>2</sup>=0.47 in Caucasians, r<sup>2</sup>=0.25 in Hispanics, and r<sup>2</sup>=0.06 in African Americans). Furthermore, <it>in silico</it> analysis suggested a lack of functional consequences for the IVS5-13insC variant.</p> <p>Conclusions</p> <p>Our results suggest that IVS5-13insC is not a functional variant and not associated with type 2 diabetes in an ethnically diverse, hypertensive, coronary artery disease population. Larger, more adequately powered studies need to be performed to confirm our findings.</p> <p>Trial registration</p> <p>clinicaltrials.gov (NCT00133692)</p>http://www.translational-medicine.com/content/11/1/12HMGA1Type 2 diabetesGenetics |
| spellingShingle | Karnes Jason H Langaee Taimour Y McDonough Caitrin W Chang Shin-Wen Ramos Miguel Catlin Jr James R Casanova Octavio E Gong Yan Pepine Carl J Johnson Julie A Cooper-DeHoff Rhonda M Lack of association of the <it>HMGA1</it> IVS5-13insC variant with type 2 diabetes in an ethnically diverse hypertensive case control cohort Journal of Translational Medicine HMGA1 Type 2 diabetes Genetics |
| title | Lack of association of the <it>HMGA1</it> IVS5-13insC variant with type 2 diabetes in an ethnically diverse hypertensive case control cohort |
| title_full | Lack of association of the <it>HMGA1</it> IVS5-13insC variant with type 2 diabetes in an ethnically diverse hypertensive case control cohort |
| title_fullStr | Lack of association of the <it>HMGA1</it> IVS5-13insC variant with type 2 diabetes in an ethnically diverse hypertensive case control cohort |
| title_full_unstemmed | Lack of association of the <it>HMGA1</it> IVS5-13insC variant with type 2 diabetes in an ethnically diverse hypertensive case control cohort |
| title_short | Lack of association of the <it>HMGA1</it> IVS5-13insC variant with type 2 diabetes in an ethnically diverse hypertensive case control cohort |
| title_sort | lack of association of the it hmga1 it ivs5 13insc variant with type 2 diabetes in an ethnically diverse hypertensive case control cohort |
| topic | HMGA1 Type 2 diabetes Genetics |
| url | http://www.translational-medicine.com/content/11/1/12 |
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