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

Frequency of the G/G Genotype of Resistin Single Nucleotide Polymorphism at −420 Appears to Be Increased in Younger-Onset Type 2 Diabetes Masaaki Ochi 1 , Haruhiko Osawa 1 , Yushi Hirota 2 , Kazuo Hara 3 , Yasuharu Tabara 4 , Yoshiharu Tokuyama 5 , Ikki Shimizu 6 , Azuma Kanatsuka 5 , Yasuhisa Fujii 6 , Jun Ohashi 7 , Tetsuro Miki 8 , Naoto Nakamura 9 , Takashi Kadowaki 3 , Mitsuo Itakura 10 , Masato Kasuga 2 and Hideichi Makino 1 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 Abstract OBJECTIVE— Resistin is an adipocyte-secreted cytokine associated with insulin resistance in mice. We previously reported that the G/G genotype of a resistin single nucleotide polymorphism (SNP) at −420 increases type 2 diabetes susceptibility by enhancing its promoter activity. The aim of the present study was to determine the relevance of SNP −120 in a large number of subjects. RESEARCH DESIGN AND METHODS— We examined 2,610 type 2 diabetic case and 2,502 control subjects. The relation between SNP −420 and the age of type 2 diabetes onset was further analyzed by adding 237 type 2 diabetic subjects with age of onset ≤40 years. RESULTS— When analyzed without considering subject age, the SNP −420 geno