P2 promoter variants of the hepatocyte nuclear factor 4alpha gene are associated with type 2 diabetes in Mexican Americans.

@article{citeulike:2192629, abstract = {Common and rare variants of the hepatocyte nuclear factor 4alpha (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 approximately 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.}, address = {Department of Medicine/Clinical Epidemiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. lehman@uthscsa.edu}, author = {Lehman, D. M. and Richardson, D. K. and Jenkinson, C. P. and Hunt, K. J. and Dyer, T. D. and Leach, R. J. and Arya, R. and Abboud, H. E. and Blangero, J. and Duggirala, R. and Stern, M. P. }, citeulike-article-id = {2192629}, doi = {http://dx.doi.org/10.2337/db06-0881}, issn = {0012-1797}, journal = {Diabetes}, keywords = {diabetes, hnf4, mapping}, month = {February}, number = {2}, pages = {513--517}, posted-at = {2008-01-03 23:27:56}, priority = {2}, title = {P2 promoter variants of the hepatocyte nuclear factor 4alpha gene are associated with type 2 diabetes in Mexican Americans.}, url = {http://dx.doi.org/10.2337/db06-0881}, volume = {56}, year = {2007} }

TY - JOUR ID - citeulike:2192629 L3 - citeulike-article-id:2192629 TI - P2 promoter variants of the hepatocyte nuclear factor 4alpha gene are associated with type 2 diabetes in Mexican Americans. JF - Diabetes VL - 56 IS - 2 SP - 513 EP - 517 AD - Department of Medicine/Clinical Epidemiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. lehman@uthscsa.edu SN - 0012-1797 N2 - Common and rare variants of the hepatocyte nuclear factor 4alpha (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 approximately 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. KW - diabetes KW - hnf4 KW - mapping AU - Lehman, DM AU - Richardson, DK AU - Jenkinson, CP AU - Hunt, KJ AU - Dyer, TD AU - Leach, RJ AU - Arya, R AU - Abboud, HE AU - Blangero, J AU - Duggirala, R AU - Stern, MP PY - 2007/02// UR - http://dx.doi.org/10.2337/db06-0881 ER -