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The frequency of the G/G genotype of resistin single nucleotide polymorphism at -420 appears to be increased in younger onset type 2 diabetes

¹ Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine
² Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine
³ Department of Metabolic Diseases, Graduate School of Medicine, The University of Tokyo
⁴ Department of Basic Medical Research and Education, Ehime University Graduate School of Medicine
⁵ Chiba Central Medical Center
⁶ Ehime Prefectural Hospital
⁷ Department of Human Genetics, School of International Health, Graduate School of Medicine, The University of Tokyo
⁸ Department of Geriatric Medicine, Ehime University Graduate School of Medicine
⁹ Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science
¹⁰ Institute for Genome Research, Division of Genetic Information, The University of Tokushima

Objective: Resistin is an adipocyte-secreted hormone associated with insulin resistance in mice. We reported that the G/G genotype of a resistin single nucleotide polymorphism (SNP) at -420 increases type 2 diabetes (T2DM) susceptibility by enhancing its promoter activity.

Research Design and Methods: To determine the relevance of SNP-420 in a large number of subjects, we examined 2610 T2DM cases and 2502 controls. The relation between SNP-420 and the age of T2DM onset was further analyzed by adding 237 T2DM subjects with the age of onset 40 or younger.

Results: When analyzed without considering subject age, the SNP-420 genotype was not associated with T2DM. Since we reported that the onset of T2DM was earlier in G/G genotype, we analyzed the data using trend test for age intervals of 10 years. The frequency of G/G genotype differed among age grades in T2DM (P=0.037), and appeard to be higher in younger grades. In T2DM, G/G genotype was more frequent in subjects younger than 40 years than in those who were 40 or older (G/G vs C/C, P=0.003). In a total of 2430 T2DM subjects with the age of onset younger than 60, the trend test showed that the G/G genotype had an increasing linear trend as the age grade of T2DM onset became younger (P=0.0379). In controls, the frequency of C/G genotype showed an increasing linear trend with increasing age (P=0.010).

Conclusions: The G/G genotype frequency of resistin SNP-420 appears to be increased in younger onset T2DM subjects.

Correspondence: hidemak{at}m.ehime-u.ac.jp

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