Frequency of the G/G Genotype of Resistin Single Nucleotide Polymorphism at  420 Appears to Be Increased in Younger-Onset Type 2 Diabetes

doi:10.2337/db06-1157

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Frequency of the G/G Genotype of Resistin Single Nucleotide Polymorphism at –420 Appears to Be Increased in Younger-Onset Type 2 Diabetes

Masaaki Ochi¹, Haruhiko Osawa¹, Yushi Hirota², Kazuo Hara³, Yasuharu Tabara⁴, Yoshiharu Tokuyama⁵, Ikki Shimizu⁶, Azuma Kanatsuka⁵, Yasuhisa Fujii⁶, Jun Ohashi⁷, Tetsuro Miki⁸, Naoto Nakamura⁹, Takashi Kadowaki³, Mitsuo Itakura¹⁰, Masato Kasuga², and Hideichi Makino¹

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

Address correspondence and reprint requests to Haruhiko Osawa or Hideichi Makino, Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan. E-mail: harosawa{at}m.ehime-u.ac.jp or hidemak{at}m.ehime-u.ac.jp

Abbreviations: PPAR, peroxisome proliferator–activated receptor; SNP, single nucleotide polymorphism

OBJECTIVE—Resistin is an adipocyte-secreted cytokine associatedwith insulin resistance in mice. We previously reported thatthe G/G genotype of a resistin single nucleotide polymorphism(SNP) at –420 increases type 2 diabetes susceptibilityby enhancing its promoter activity. The aim of the present studywas to determine the relevance of SNP –120 in a largenumber of subjects.

RESEARCH DESIGN AND METHODS— We examined 2,610 type 2diabetic case and 2,502 control subjects. The relation betweenSNP –420 and the age of type 2 diabetes onset was furtheranalyzed by adding 237 type 2 diabetic subjects with age ofonset $≤$ 40 years.

RESULTS—When analyzed without considering subject age,the SNP –420 genotype was not associated with type 2 diabetes.Since we reported that the onset of type 2 diabetes was earlierin G/G genotype, we analyzed the data using a trend test forage intervals of 10 years. The frequency of G/G genotype differedamong age grades in type 2 diabetes (P = 0.037) and appearedto be higher in younger grades. In type 2 diabetes, G/G genotypewas more frequent in subjects aged <40 years than in thoseaged $≥$ 40 years (G/G vs. C/C, P = 0.003). In a total of 2,430type 2 diabetic subjects with age of onset <60 years, thetrend test showed that the G/G genotype had an increasing lineartrend as the age grade of type 2 diabetes onset became younger(P = 0.0379). In control subjects, the frequency of C/G genotypeshowed 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 type 2 diabeticsubjects.

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