Human Resistin Gene, Obesity, and Type 2 Diabetes
Mutation Analysis and Population Study
- Federica Sentinelli1,
- Stefano Romeo1,
- Marcello Arca2,
- Emanuela Filippi1,
- Frida Leonetti1,
- Michela Banchieri1,
- Umberto Di Mario1 and
- Marco Giorgio Baroni1
- 1Department of Clinical Sciences, Division of Endocrinology, University of Rome “La Sapienza,” Rome, Italy
- 2Institute of Terapia Medica Sistematica, University of Rome “La Sapienza,” Rome, Italy
Abstract
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 (G1326C). 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 G1326C variant and diabetes and obesity. Comparison of clinical and metabolic parameters between G1326C 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.
Footnotes
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Address correspondence and reprint requests to Marco G. Baroni, MD, PhD, Department of Clinical Sciences, II Clinica Medica, Policlinico Umberto I, University of Rome “la Sapienza,” 00161 Rome, Italy. E-mail: marco.baroni{at}uniromal.it.
Received for publication 10 August 2001 and accepted in revised form 19 November 2001.
CAD, coronary artery disease; HOMAIR, homeostasis model assessment of insulin resistance; SNP, single nucleotide substitution; SSCP, single-strand conformation polymorphism; UTR, untranslated region.
- DIABETES
