Lack of association of the HMGA1 IVS5-13insC variant with type 2 diabetes in an ethnically diverse hypertensive case control cohort
详细信息 查看全文
- 作者：Jason H Karnes (1) (2)
Taimour Y Langaee (2)
Caitrin W McDonough (2)
Shin-Wen Chang (2)
Miguel Ramos (2)
James R Catlin Jr (2)
Octavio E Casanova (2)
Yan Gong (2)
Carl J Pepine (3)
Julie A Johnson (2) (3)
Rhonda M Cooper-DeHoff (2) (3) - 关键词：HMGA1 ; Type 2 diabetes ; Genetics
- 刊名：Journal of Translational Medicine
- 出版年：2013
- 出版时间：December 2013
- 年：2013
- 卷：11
- 期：1
- 全文大小：240KB
- 参考文献：1. Zhang P, Zhang X, Brown J, Vistisen D, Sicree R, Shaw J, Nichols G:
2. Herder C, Roden M:
3. Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G, / et al.:
4. Talmud PJ, Hingorani AD, Cooper JA, Marmot MG, Brunner EJ, Kumari M, Kivimaki M, Humphries SE:
5. Chiefari E, Tanyolac S, Paonessa F, Pullinger CR, Capula C, Iiritano S, Mazza T, Forlin M, Fusco A, Durlach V, / et al.:
6. Liu L, Ding H, Wang HR, Xu YJ, Cui GL, Wang PH, Yuan G, Yu XF, Wang DW:
7. Marquez M, Huyvaert M, Perry JR, Pearson RD, Falchi M, Morris AP, Vivequin S, Lobbens S, Yengo L, Gaget S, / et al.:
8. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, / et al.:
9. Pepine CJ, Handberg-Thurmond E, Marks RG, Conlon M, Cooper-DeHoff R, Volkers P, Zellig P:
10. Pepine CJ, Handberg EM, Cooper-DeHoff RM, Marks RG, Kowey P, Messerli FH, Mancia G, Cangiano JL, Garcia-Barreto D, Keltai M, / et al.:
11. Cooper-Dehoff R, Cohen JD, Bakris GL, Messerli FH, Erdine S, Hewkin AC, Kupfer S, Pepine CJ:
12. Cooper-DeHoff RM, Handberg EM, Mancia G, Zhou Q, Champion A, Legler UF, Pepine CJ:
13. Keating BJ, Tischfield S, Murray SS, Bhangale T, Price TS, Glessner JT, Galver L, Barrett JC, Grant SF, Farlow DN, / et al.:
14. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC:
15. Pritchard JK, Stephens M, Donnelly P:
16. Cooper-DeHoff RM, Aranda JM Jr, Gaxiola E, Cangiano JL, Garcia-Barreto D, Conti CR, Hewkin A, Pepine CJ:
17. Barrett JC, Fry B, Maller J, Daly MJ:
18. Chelala C, Khan A, Lemoine NR:
19. Cartegni L, Wang J, Zhu Z, Zhang MQ, Krainer AR:
20. Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Samani NJ, / et al.:
21. Froguel P, Marquez M, Cauchi S:
22. Goldman N, Lin IF, Weinstein M, Lin YH:
23. Aguilar D, Solomon SD, Kober L, Rouleau JL, Skali H, McMurray JJ, Francis GS, Henis M, O’Connor CM, Diaz R, / et al.:
24. Bosch J, Lonn E, Pogue J, Arnold JM, Dagenais GR, Yusuf S:
25. Yusuf S, Gerstein H, Hoogwerf B, Pogue J, Bosch J, Wolffenbuttel BH, Zinman B:
26. Saxena R, Elbers CC, Guo Y, Peter I, Gaunt TR, Mega JL, Lanktree MB, Tare A, Castillo BA, Li YR, / et al.: - 作者单位：Jason H Karnes (1) (2)
Taimour Y Langaee (2)
Caitrin W McDonough (2)
Shin-Wen Chang (2)
Miguel Ramos (2)
James R Catlin Jr (2)
Octavio E Casanova (2)
Yan Gong (2)
Carl J Pepine (3)
Julie A Johnson (2) (3)
Rhonda M Cooper-DeHoff (2) (3)
1. Division of Clinical Pharmacology, Vanderbilt University, 1275 Medical Research Building IV, Nashville, TN, 37232-0575, USA
2. Department of Pharmacotherapy and Translational Research, University of Florida, HSC PO Box 100486, Gainesville, FL, 32610-0486, USA
3. Division of Cardiovascular Medicine, University of Florida, PO Box 100277, Gainesville, FL, 32610-0486, USA
文摘
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)