TY - JOUR
T1 - Lack of association of the HMGA1 IVS5-13insC variant with type 2 diabetes in an ethnically diverse hypertensive case control cohort
AU - Karnes, Jason H.
AU - Langaee, Taimour Y.
AU - McDonough, Caitrin W.
AU - Chang, Shin Wen
AU - Ramos, Miguel
AU - Catlin, James R.
AU - Casanova, Octavio E.
AU - Gong, Yan
AU - Pepine, Carl J.
AU - Johnson, Julie A.
AU - Cooper-DeHoff, Rhonda M.
N1 - Funding Information:
This study was funded by NIH grant U01 GM074492, R01 HL74730, HL086558 (RCD), and TL1RR029888 (JHK), and grants from Abbott Laboratories and the University of Florida Opportunity Fund. We thank Ben Burkley, Lynda Stauffer, and Cheryl Galloway for processing and genotyping samples.
PY - 2013/1/9
Y1 - 2013/1/9
N2 - Background: Recently, the high-mobility group A1 gene (HMGA1) 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 HMGA1-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).Methods: 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 HMGA1 single nucleotide polymorphisms (SNPs) was performed using the Illumina® HumanCVD BeadChip. We used logistic regression to test association of the HMGA1 IVS5-13insC and diabetes, adjusted for age, gender, body mass index, and percentage European, African, and Native American ancestry.Results: 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 (r2) of IVS5-13insC and rs9394200, a SNP previously used as a tag SNP for IVS5-13insC, was low (r2=0.47 in Caucasians, r2=0.25 in Hispanics, and r2=0.06 in African Americans). Furthermore, in silico analysis suggested a lack of functional consequences for the IVS5-13insC variant.Conclusions: 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.Trial registration: clinicaltrials.gov (NCT00133692).
AB - Background: Recently, the high-mobility group A1 gene (HMGA1) 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 HMGA1-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).Methods: 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 HMGA1 single nucleotide polymorphisms (SNPs) was performed using the Illumina® HumanCVD BeadChip. We used logistic regression to test association of the HMGA1 IVS5-13insC and diabetes, adjusted for age, gender, body mass index, and percentage European, African, and Native American ancestry.Results: 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 (r2) of IVS5-13insC and rs9394200, a SNP previously used as a tag SNP for IVS5-13insC, was low (r2=0.47 in Caucasians, r2=0.25 in Hispanics, and r2=0.06 in African Americans). Furthermore, in silico analysis suggested a lack of functional consequences for the IVS5-13insC variant.Conclusions: 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.Trial registration: clinicaltrials.gov (NCT00133692).
KW - Genetics
KW - HMGA1
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=84872025494&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84872025494&partnerID=8YFLogxK
U2 - 10.1186/1479-5876-11-12
DO - 10.1186/1479-5876-11-12
M3 - Article
C2 - 23302499
AN - SCOPUS:84872025494
VL - 11
JO - Journal of Translational Medicine
JF - Journal of Translational Medicine
SN - 1479-5876
IS - 1
M1 - 12
ER -