Lack of association of the HMGA1 IVS5-13insC variant with type 2 diabetes in an ethnically diverse hypertensive case control cohort

Jason H. Karnes, Taimour Y. Langaee, Caitrin W. McDonough, Shin Wen Chang, Miguel Ramos, James R. Catlin, Octavio E. Casanova, Yan Gong, Carl J. Pepine, Julie A. Johnson, Rhonda M. Cooper-DeHoff

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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).

Original languageEnglish (US)
Article number12
JournalJournal of Translational Medicine
Volume11
Issue number1
DOIs
StatePublished - Jan 9 2013
Externally publishedYes

Keywords

  • Genetics
  • HMGA1
  • Type 2 diabetes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Lack of association of the HMGA1 IVS5-13insC variant with type 2 diabetes in an ethnically diverse hypertensive case control cohort'. Together they form a unique fingerprint.

  • Cite this

    Karnes, J. H., Langaee, T. Y., McDonough, C. W., Chang, S. W., Ramos, M., Catlin, J. R., Casanova, O. E., Gong, Y., Pepine, C. J., Johnson, J. A., & Cooper-DeHoff, R. M. (2013). Lack of association of the HMGA1 IVS5-13insC variant with type 2 diabetes in an ethnically diverse hypertensive case control cohort. Journal of Translational Medicine, 11(1), [12]. https://doi.org/10.1186/1479-5876-11-12