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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.
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