The 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 Osawa (harosawa{at}m.ehime-u.ac.jp)1,
- 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 Makino (hidemak{at}m.ehime-u.ac.jp)1
- 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
Abstract
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.
Footnotes
-
- Received August 17, 2006.
- Accepted August 8, 2007.
- Copyright © American Diabetes Association
