This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hamaguchi, K. Articles by Sakata, T. Search for Related Content PubMed PubMed Citation Articles by Hamaguchi, K. Articles by Sakata, T.

The PC-1 Q121 Allele Is Exceptionally Prevalent in the Dominican Republic and Is Associated with Type 2 Diabetes

Department of Internal Medicine I, Faculty of Medicine (K.H., Y.K., T.Y., H.Y.), and Department of Health Science Center (H.T.), Oita University, Oita 879-5593, Japan; Instituto Nacional de Diabetes, Endocrinología y Nutrición (J.A.H.B.), Universidad Technologica de Santiago (M.C.LL.), Universidad Autónoma de Santo Domingo (L.I.B.V.), and Centro de Gastroenterologia (B.J.W.), Santo Domingo, Dominican Republic; and Graduate School of Health and Nutritional Sciences, Nakamura Gakuen University (T.S.), Fukuoka 814-0198, Japan

Address all correspondence and requests for reprints to: Toshiie Sakata, M.D., Ph.D., Faculty of Nutritional Sciences, Nakamura Gakuen University, 5-7-1 Befu, Jounan-Ku, Fukuoka, 814-0198, Japan. E-mail: sakata{at}cc.nakamura-u.ac.jp.

The human glycoprotein PC-1 codon Q121 allele has been correlated with insulin resistance, but not with type 2 diabetes or obesity. We investigated the prevalence of PC-1 Q121 in the Dominican Republic population (755 subjects studied) and whether this variant is associated with insulin resistance, obesity, or type 2 diabetes. The prevalence of PC-1 Q121 was high compared with that in other populations. The proportions of genotypes detected were: KK, 21.6%; KQ, 48.3%; and QQ, 30.1%. This compares to approximately 74%, 24%, and 2% in other populations. Among nonobese, nondiabetic subjects, the insulin response of KQ (P = 0.027) and QQ (P = 0.031) subjects was greater during the oral glucose tolerance test than that of KK subjects, whereas plasma glucose profiles were comparable. The Q allele was more prevalent in obese type 2 diabetics than in controls (P = 0.026; odds ratio = 1.56). Multiple regression analysis, after adjusting for age, gender, and body mass index, showed the QQ genotype to be associated with type 2 diabetes (P = 0.043; odds ratio = 2.74), but not obesity (P = 0.068). These results indicate that the PC-1 Q121 allele is exceptionally prevalent in the Dominican Republic, contributing to both insulin resistance and type 2 diabetes.

This work was supported by Grants-in-Aid for Scientific Research 10045072 and 13576024 (to T.S.), 15406035 (to H.Y.), and 14571102 (to K.H.) from the Ministry of Education, Culture, Sports, Science, and Technology (1998) and the Japan Society for the Promotion of Science (1999–2004), Japan.

Abbreviations: ANCOVA, Analysis of covariance; AUC, area under the curve; BMI, body mass index; CI, confidence interval; HOMA-ß, homeostasis model assessment-ß cell function; HOMA-R, homeostasis model assessment-insulin resistance; IRI, immunoreactive insulin; ISI-comp, insulin sensitivity index composite; K, lysine; OGTT, oral glucose tolerance test; OR, odds ratio; PAR%, population-attributable risk percentage; PG, plasma glucose; Q, glutamine.

This article has been cited by other articles:

				L. S.-H. Wu, C.-H. Hsieh, D. Pei, Y.-J. Hung, S.-W. Kuo, and E. Lin Association and interaction analyses of genetic variants in ADIPOQ, ENPP1, GHSR, PPAR{gamma} and TCF7L2 genes for diabetic nephropathy in a Taiwanese population with type 2 diabetes Nephrol. Dial. Transplant., June 8, 2009; (2009) gfp271v1. [Abstract] [Full Text] [PDF]

				A. F. Moore, K. A. Jablonski, C. C. Mason, J. B. McAteer, R. F. Arakaki, B. J. Goldstein, S. E. Kahn, A. E. Kitabchi, R. L. Hanson, W. C. Knowler, et al. The Association of ENPP1 K121Q with Diabetes Incidence Is Abolished by Lifestyle Modification in the Diabetes Prevention Program J. Clin. Endocrinol. Metab., February 1, 2009; 94(2): 449 - 455. [Abstract] [Full Text] [PDF]

				T Dwyer, L Blizzard, B Patterson, A-L Ponsonby, K Martin, S Quinn, M M Sale, S M Richards, R Morley, S Rich, et al. Association between birth weight and adolescent systolic blood pressure in a caucasian birth cohort differs according to skin type, CRH promoter or 11{beta}-HSD2 genotype Arch. Dis. Child., September 1, 2008; 93(9): 760 - 767. [Abstract] [Full Text] [PDF]

				J. B. McAteer, S. Prudente, S. Bacci, H. N. Lyon, J. N. Hirschhorn, V. Trischitta, J. C. Florez, and for the ENPP1 Consortium The ENPP1 K121Q Polymorphism Is Associated With Type 2 Diabetes in European Populations: Evidence From an Updated Meta-Analysis in 42,042 Subjects Diabetes, April 1, 2008; 57(4): 1125 - 1130. [Abstract] [Full Text] [PDF]

				K. L. Keene, J. C. Mychaleckyj, S. G. Smith, T. S. Leak, P. S. Perlegas, C. D. Langefeld, B. I. Freedman, S. S. Rich, D. W. Bowden, and M. M. Sale Association of the Distal Region of the Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 Gene With Type 2 Diabetes in an African-American Population Enriched for Nephropathy Diabetes, April 1, 2008; 57(4): 1057 - 1062. [Abstract] [Full Text] [PDF]

				I. D. Goldfine, B. A. Maddux, J. F. Youngren, G. Reaven, D. Accili, V. Trischitta, R. Vigneri, and L. Frittitta The Role of Membrane Glycoprotein Plasma Cell Antigen 1/Ectonucleotide Pyrophosphatase Phosphodiesterase 1 in the Pathogenesis of Insulin Resistance and Related Abnormalities Endocr. Rev., February 1, 2008; 29(1): 62 - 75. [Abstract] [Full Text] [PDF]

				C. J. Willer, L. L. Bonnycastle, K. N. Conneely, W. L. Duren, A. U. Jackson, L. J. Scott, N. Narisu, P. S. Chines, A. Skol, H. M. Stringham, et al. Screening of 134 Single Nucleotide Polymorphisms (SNPs) Previously Associated With Type 2 Diabetes Replicates Association With 12 SNPs in Nine Genes Diabetes, January 1, 2007; 56(1): 256 - 264. [Abstract] [Full Text] [PDF]

				J. Bochenski, G. Placha, K. Wanic, M. Malecki, J. Sieradzki, J. H. Warram, and A. S. Krolewski New Polymorphism of ENPP1 (PC-1) Is Associated With Increased Risk of Type 2 Diabetes Among Obese Individuals Diabetes, September 1, 2006; 55(9): 2626 - 2630. [Abstract] [Full Text] [PDF]

				S. Bacci, O. Ludovico, S. Prudente, Y.-Y. Zhang, R. Di Paola, D. Mangiacotti, A. Rauseo, D. Nolan, J. Duffy, G. Fini, et al. 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 Diabetes, October 1, 2005; 54(10): 3021 - 3025. [Abstract] [Full Text] [PDF]

				N. Abate, M. Chandalia, P. Satija, B. Adams-Huet, S. M. Grundy, S. Sandeep, V. Radha, R. Deepa, and V. Mohan ENPP1/PC-1 K121Q Polymorphism and Genetic Susceptibility to Type 2 Diabetes Diabetes, April 1, 2005; 54(4): 1207 - 1213. [Abstract] [Full Text] [PDF]