Ethnic differences in the frequency of ENPP1/PC1 121Q genetic variant in the Dallas Heart Study cohort

被引:40
作者
Chandalia, Manisha
Grundy, Scott M.
Adams-Huet, Beverley
Abate, Nicola
机构
[1] Univ Texas, SW Med Ctr, Div Endocrinol & Metab, Dallas, TX 75390 USA
[2] Univ Texas, SW Med Ctr, Ctr Human Nutr, Dept Med, Dallas, TX 75390 USA
[3] Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA
[4] Univ Texas, SW Med Ctr, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75390 USA
[5] Univ Texas, SW Med Ctr, Dept Clin Sci, Dallas, TX 75216 USA
[6] Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75216 USA
关键词
type; 2; diabetes; insulin resistance; ethnicity; ENPP1; PC-1;
D O I
10.1016/j.jdiacomp.2006.11.003
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Genetic susceptibility modulates the impact of obesity on the risk for type 2 diabetes. One candidate gene predisposing to type 2 diabetes is ENPP1/PC1. A common polymorphism in this protein, K121Q, is associated with insulin resistance and increased susceptibility to type 2 diabetes in Caucasian, Afro-Caribbean, and South Asian populations. The goal of this study was to evaluate differences in the prevalence of the ENPP1 121Q variant in the Caucasian, African-American, and Hispanic populations in Dallas county and to establish a population-based estimate of gene variant prevalence for future investigations. We also evaluated the association between the ENPP1 121Q variant and diabetes. The Dallas Heart Study (DHS) is a multiethnic probability-based sample of the Dallas county population in which African-Americans were systematically oversampled so that the final sample was 50% African-Americans. We performed ENPP1/PC1 genotyping in 1038 non-Hispanic Whites (544 women, 494 men), 1815 African-Americans (1052 women and 763 men), and 597 Hispanics (347 women, 250 men). The frequency of ENPP1/PC1 K121Q was higher in both African-Americans (78.5%) and Hispanics (21.9%) than in the non-Hispanic White group (13.2%). The former two groups also have a higher prevalence of type 2 diabetes (African-Americans, 14.1%, and Hispanics, 11.7%) compared to non-Hispanic Whites (6.8%). Logistic regression analysis revealed significant interactions between the ENPP1 genotype, age, and body mass index within each ethnic group. After adjustment for these variables and their interactions, ENPP1 Q allele predicted diabetes when a recessive model was tested. Ethnic differences in ENPP1 121Q allele frequency may contribute to the increased susceptibility to type 2 diabetes observed in US minority groups. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:143 / 148
页数:6
相关论文
共 36 条
[1]   The impact of ethnicity on type 2 diabetes [J].
Abate, N ;
Chandalia, M .
JOURNAL OF DIABETES AND ITS COMPLICATIONS, 2003, 17 (01) :39-58
[2]   ENPP1/PC-1 K121Q polymorphism and genetic susceptibility to type 2 diabetes [J].
Abate, N ;
Chandalia, M ;
Satija, P ;
Adams-Huet, B ;
Grundy, SM ;
Sandeep, S ;
Radha, V ;
Deepa, R ;
Mohan, V .
DIABETES, 2005, 54 (04) :1207-1213
[3]   Genetic polymorphism PC-1K121Q and ethnic susceptibility to insulin resistance [J].
Abate, N ;
Carulli, L ;
Cabo-Chan, A ;
Chandalia, M ;
Snell, PG ;
Grundy, SM .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2003, 88 (12) :5927-5934
[4]   The K121Q polymorphism of the ENPP1/PC-1 gene is associated with insulin resistance/atherogenic phenotypes, including earlier onset of type 2 diabetes and myocardial infarction [J].
Bacci, S ;
Ludovico, O ;
Prudente, S ;
Zhang, YY ;
Di Paola, R ;
Mangiacotti, D ;
Rauseo, A ;
Nolan, D ;
Duffy, J ;
Fini, G ;
Salvemini, L ;
Amico, C ;
Vigna, C ;
Pellegrini, F ;
Menzaghi, C ;
Doria, A ;
Trischitta, V .
DIABETES, 2005, 54 (10) :3021-3025
[5]   New polymorphism of ENPP1 (PC-1) is associated with increased risk of type 2 diabetes among obese individuals [J].
Bochenski, Jacek ;
Placha, Grzegorz ;
Wanic, Krzysztof ;
Malecki, Maciej ;
Sieradzki, Jacek ;
Warram, James H. ;
Krolewski, Andrzej S. .
DIABETES, 2006, 55 (09) :2626-2630
[6]   The Q allele variant (GLN121) of membrane glycoprotein PC-1 interacts with the insulin receptor and inhibits insulin signaling more effectively than the common K allele variant (LYS121) [J].
Costanzo, BV ;
Trischitta, V ;
Di Paola, R ;
Spampinato, D ;
Pizzuti, A ;
Vigneri, R ;
Frittitta, L .
DIABETES, 2001, 50 (04) :831-836
[7]   Increased hepatic levels of the insulin receptor inhibitor, PC-1/NPP1, induce insulin resistance and glucose intolerance [J].
Dong, HJ ;
Maddux, BA ;
Altomonte, J ;
Meseck, M ;
Accili, D ;
Terkeltaub, R ;
Johnson, K ;
Youngren, JF ;
Goldfine, ID .
DIABETES, 2005, 54 (02) :367-372
[8]   PC-1 content in skeletal muscle of non-obese, non-diabetic subjects: Relationship to insulin receptor tyrosine kinase and whole body insulin sensitivity [J].
Frittitta, L ;
Youngren, J ;
Vigneri, R ;
Maddux, BA ;
Trischitta, V ;
Goldfine, ID .
DIABETOLOGIA, 1996, 39 (10) :1190-1195
[9]   Elevated PC-1 content in cultured skin fibroblasts correlates with decreased in vivo and in vitro insulin action in nondiabetic subjects - Evidence that PC-1 may be an intrinsic factor in impaired insulin receptor signaling [J].
Frittitta, L ;
Spampinato, D ;
Solini, A ;
Nosadini, R ;
Goldfine, ID ;
Vigneri, R ;
Trischitta, V .
DIABETES, 1998, 47 (07) :1095-1100
[10]   Increased adipose tissue PC-1 protein content, but not tumour necrosis factor-alpha gene expression, is associated with a reduction of both whole body insulin sensitivity and insulin receptor tyrosine-kinase activity [J].
Frittitta, L ;
Youngren, JF ;
Sbraccia, P ;
DAdamo, M ;
Buongiorno, A ;
Vigneri, R ;
Goldfine, ID ;
Trischitta, V .
DIABETOLOGIA, 1997, 40 (03) :282-289