P2 Promoter Variants of the Hepatocyte Nuclear Factor 4α Gene Are Associated With Type 2 Diabetes in Mexican Americans
- Donna M. Lehman1,
- Dawn K. Richardson2,
- Chris P. Jenkinson2,
- Kelly J. Hunt1,
- Thomas D. Dyer3,
- Robin J. Leach4,
- Rector Arya1,
- Hanna E. Abboud5,
- John Blangero3,
- Ravindranath Duggirala3 and
- Michael P. Stern1
- 1Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas
- 2Diabetes Division, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas
- 3Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas
- 4Departments of Cellular and Structural Biology and Pediatrics, University of Texas Health Science Center, San Antonio, Texas
- 5Division of Nephrology, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas
- Address correspondence and reprint requests to Donna M. Lehman, Department of Medicine/Clinical Epidemiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229. E-mail: lehman{at}uthscsa.edu
Abstract
Common and rare variants of the hepatocyte nuclear factor 4α (HNF4A) gene have been associated with type 2 diabetes and related traits in several populations suggesting the involvement of this transcription factor in diabetes pathogenesis. Single nucleotide polymorphisms (SNPs) within a large haplotype block surrounding the alternate P2 promoter, located ∼45 kb upstream from the coding region, have been investigated in several populations of varying ethnicity with inconsistent results. Additionally, SNPs located within the P1 promoter and coding region have also been inconsistently associated with type 2 diabetes. Characterization of variation across this gene region in Mexican-American populations has not been reported. We therefore examined polymorphisms across the HNF4A gene in a cohort of Mexican-American pedigrees and assessed their association with type 2 diabetes. We observed evidence for association of SNPs in the P2 promoter region with type 2 diabetes (P = 0.003) and its age at diagnosis (P = 0.003). The risk allele frequency (53%) was intermediate to that reported in Caucasian populations (20–27%) and Pima Indians (83%). No other SNPs were associated with either trait. These results support the possibility that a variant in the P2 promoter region of HNF4A, or variants in linkage disequilibrium within this region, contributes to susceptibility to type 2 diabetes in many ethnic populations including Mexican Americans.
- LD, linkage disequilibrium
- SAFDGS, San Antonio Family Diabetes and Gallbladder Studies
- SNP, single nucleotide polymorphism
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted October 23, 2006.
- Received June 29, 2006.
- DIABETES
