The Gly146Ala variation in human SF-1 gene: its association with insulin resistance and type 2 diabetes in Chinese.
OBJECTIVE
While steroidogenic factor 1 (SF-1) is traditionally an essential nuclear receptor for steroidogenic tissues, current emerging studies revealed that the receptor is also closely implicated in metabolism. Mutations of SF-1 gene cause metabolic disorders like obesity in both human and mice. The aim of the present study is to examine whether the Gly146Ala variation in the gene for SF-1, that is known to impair SF-1 function and related to adrenal disorders, affects susceptibility to type 2 diabetes.


METHODS
Hundred and fifty-one type 2 diabetic subjects and 141 non-diabetic control subjects of Han Chinese were recruited and the SF-1 genotype were analyzed by PCR-RFLP method.


RESULTS
The Gly146Ala variation occurs frequently in the Han Chinese. Allele Ala frequency in the control subjects (27.3%) was significantly lower than that in type 2 diabetic subjects (37.1%, chi2=6.37, p=0.01). The Gly/Ala and Ala/Ala genotypes frequencies were also higher in diabetic subjects. In both the diabetic and control populations, subjects carrying allele Ala, as compared to those not, had higher fasting insulin levels and higher HOMA values.


CONCLUSIONS
The SF-1 Gly146Ala variation may constitute a susceptible factor for development of type 2 diabetes and impairment of insulin actions.
Department of Medicine and Endocrinology, Renji Hospital, Shanghai 2nd Medical University, PuDong, Shanghai, China.
Wei
W
Liu
Min
M
Liu
WuQiang
W
Fan
Hajime
H
Nawata
Toshihiko
T
Yanase
D000409:Alanine / Q000235:genetics; D016009:Chi-Square Distribution; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005998:Glycine / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000235:genetics*
D018398:Homeodomain Proteins; C515057:NR5A1 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D000409:Alanine; D005998:Glycine