Journal Article

Molecular scanning of the human sorbin and SH3-domain-containing-1 (<i>SORBS1</i>) gene: positive association of the T228A polymorphism with obesity and type 2 diabetes

Wen-Hsing Lin, Ken C. Chiu, Hui-Min Chang, Kuan-Chin Lee, Tong-Yuan Tai and Lee-Ming Chuang

in Human Molecular Genetics

Volume 10, issue 17, pages 1753-1760
Published in print August 2001 | ISSN: 0964-6906
Published online August 2001 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/10.17.1753
Molecular scanning of the human sorbin and  SH3-domain-containing-1 (SORBS1) gene: positive association of the T228A polymorphism with obesity and type 2 diabetes

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In the mouse, the SH3P12 or the c-Cbl-associated protein (CAP) has been shown as an important signaling molecule in insulin-stimulated glucose uptake. The human homolog for the sorbin and SH3-domain-containing-1 gene, termed SORBS1, might play a role in human disorders with insulin resistance. To explore the genetic role of SORBS1 in human obesity and type 2 diabetes, we investigated the nucleotide polymorphisms in the SORBS1 gene with molecular scanning. After scanning for a total of 13 136 bp in each of 40 chromosomes, we have identified 14 single nucleotide polymorphisms (SNPs) in the human SORBS1 gene. Among them, two SNPs affected amino acid coding (R74W and T228A), four occurred within exons but did not affect amino acid coding, and the remaining eight occurred within introns, which were located outside of the consensus region of the splicing mechanism. Further studies in 202 non-obese, 113 obese and 455 subjects with type 2 diabetes revealed that the A-allele of the T228A polymorphism in exon 7 exerted a protective role for both obesity [relative risk 0.466; 95% confidence interval (95% CI) 0.265–0.821] and diabetes (relative risk 0.668; 95% CI 0.472–0.945). Neither allele of the R74W polymorphism was associated with either obesity or diabetes. In conclusion, our results suggest that the A228 allele of the T228A polymorphism of the SORBS1 gene is a protective factor for both obesity and diabetes, and also imply that the SORBS1 gene plays an important role in the pathogenesis of human disorders with insulin resistance.

Journal Article.  5406 words.  Illustrated.

Subjects: Genetics and Genomics

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