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

  1. Masaaki Ochi1,
  2. Haruhiko Osawa1,
  3. Yushi Hirota2,
  4. Kazuo Hara3,
  5. Yasuharu Tabara4,
  6. Yoshiharu Tokuyama5,
  7. Ikki Shimizu6,
  8. Azuma Kanatsuka5,
  9. Yasuhisa Fujii6,
  10. Jun Ohashi7,
  11. Tetsuro Miki8,
  12. Naoto Nakamura9,
  13. Takashi Kadowaki3,
  14. Mitsuo Itakura10,
  15. Masato Kasuga2 and
  16. Hideichi Makino1
  1. 1Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine, Ehime, Japan
  2. 2Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
  3. 3Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
  4. 4Department of Basic Medical Research and Education, Ehime University Graduate School of Medicine, Ehime, Japan
  5. 5Diabetes Center, Chiba Central Medical Center, Chiba, Japan
  6. 6Department of Internal Medicine, Ehime Prefectural Hospital, Ehime, Japan
  7. 7Department of Human Genetics, School of International Health, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
  8. 8Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Ehime, Japan
  9. 9Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
  10. 10Division of Genetic Information, Institute for Genome Research, University of Tokushima, Tokushima, Japan
  1. 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 genotype was not associated with type 2 diabetes. Since we reported that the onset of type 2 diabetes was earlier in G/G genotype, we analyzed the data using a trend test for age intervals of 10 years. The frequency of G/G genotype differed among age grades in type 2 diabetes (P = 0.037) and appeared to be higher in younger grades. In type 2 diabetes, G/G genotype was more frequent in subjects aged <40 years than in those aged ≥40 years (G/G vs. C/C, P = 0.003). In a total of 2,430 type 2 diabetic subjects with age of onset <60 years, the trend test showed that the G/G genotype had an increasing linear trend as the age grade of type 2 diabetes onset became younger (P = 0.0379). In control subjects, 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 type 2 diabetic subjects.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 13 August 2007. DOI: 10.2337/db06-1157.

    Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db06-1157.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received August 17, 2006.
    • Accepted August 8, 2007.
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  1. Diabetes vol. 56 no. 11 2834-2838
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