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


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 <or=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 >or=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.
Ochi
Masaaki
M
Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
Osawa
Haruhiko
H
Hirota
Yushi
Y
Hara
Kazuo
K
Tabara
Yasuharu
Y
Tokuyama
Yoshiharu
Y
Shimizu
Ikki
I
Kanatsuka
Azuma
A
Fujii
Yasuhisa
Y
Ohashi
Jun
J
Miki
Tetsuro
T
Nakamura
Naoto
N
Kadowaki
Takashi
T
Itakura
Mitsuo
M
Kasuga
Masato
M
Makino
Hideichi
H
D000328:Adult; D017668:Age of Onset; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006147:Guanine; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D052243:Resistin / Q000172:deficiency / Q000235:genetics*
D052243:Resistin; D006147:Guanine