Human resistin gene, obesity, and type 2 diabetes: mutation analysis and population study.
The hormone resistin has been suggested to link obesity to type 2 diabetes by modulating steps in the insulin-signaling pathway and inducing insulin resistance. Thus, the resistin gene represents a potential candidate for the etiology of insulin resistance and type 2 diabetes. In this study, we analyzed the coding sequence of the three exons of the resistin gene, together with its 5' regulatory region and 3' untranslated region (UTR), by single-strand conformation polymorphism (SSCP) in 58 type 2 diabetic subjects, 59 obese subjects, and 60 normal subjects. Only one sequence variant was detected in the resistin gene. Sequencing of this variant revealed the presence of a single nucleotide substitution (SNP) in the 3'-UTR of exon 3 (G1326A) [corrected]. Because 3'-UTR SNPs have been shown to affect gene expression, we examined the frequency of this SNP in 591 subjects (198 obese subjects, 207 diabetic subjects, and 186 control subjects) by PCR amplification and BseRI digestion. No significant association was found between the G1326A [corrected] variant and diabetes and obesity. Comparison of clinical and metabolic parameters between G1326A [corrected] carriers and noncarriers again showed no significant difference. In conclusion, our data suggest that genetic defects of the resistin gene are unlikely to play a role in the etiology of these common disorders in our population.
Sentinelli
Federica
F
Department of Clinical Sciences, Division of Endocrinology, University of Rome La Sapienza, Rome, Italy.
Romeo
Stefano
S
Arca
Marcello
M
Filippi
Emanuela
E
Leonetti
Frida
F
Banchieri
Michela
M
Di Mario
Umberto
U
Baroni
Marco Giorgio
MG
D020413:3' Untranslated Regions; D000328:Adult; D004252:DNA Mutational Analysis; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005091:Exons; D005260:Female; D015870:Gene Expression; D006729:Hormones, Ectopic / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000032:analysis; D052243:Resistin
D020413:3' Untranslated Regions; D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; C499624:RETN protein, human; C486574:RETNLB protein, human; D012333:RNA, Messenger; D052243:Resistin; C082523:endodeoxyribonuclease BseRI; D015252:Deoxyribonucleases, Type II Site-Specific