Resequencing of genes for transforming growth factor β1 (<it>TGFB1</it>) type 1 and 2 receptors (<it>TGFBR1</it>, <it>TGFBR2</it>), and association analysis of variants with diabetic nephropathy

• Main Authors: Patterson Chris C (Author), Savage David A (Author), McKnight Amy (Author), Sadlier Denise (Author), Maxwell A Peter (Author)
• Format: Book
• Published: BMC, 2007-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/1471-2350-8-5; 1471-2350
• Keywords: Internal medicine; RC31-1245; Genetics; QH426-470
• Source: BMC Medical Genetics, Vol 8, Iss 1, p 5 (2007)

<p>Abstract</p> <p>Background</p> <p>Diabetic nephropathy is the leading cause of end stage renal failure in the western world. There is substantial epidemiological evidence supporting a genetic predisposition to diabetic nephropathy, however the exact molecular mechanisms remain unknown. Transforming growth factor (TGFβ1) is a crucial mediator in the pathogenesis of diabetic nephropathy.</p> <p>Methods</p> <p>We investigated the role of five known single nucleotide polymorphisms (SNPs) in the <it>TGFB1 </it>gene for their association with diabetic nephropathy in an Irish, type 1 diabetic case (n = 272) control (n = 367) collection. The activity of TGFβ1 is facilitated by the action of type 1 and type 2 receptors, with both receptor genes (<it>TGFBR1 </it>and <it>TGFBR2</it>) shown to be upregulated in diabetic kidney disease. We therefore screened <it>TGFBR1 </it>and <it>TGFBR2 </it>genes for genomic variants using WAVE™ (dHPLC) technology and confirmed variants by direct capillary sequencing. Allele frequencies were determined in forty-eight healthy individuals. Data for all SNPs was assessed for Hardy Weinberg equilibrium, with genotypes and allele frequencies compared using the χ²test for contingency tables. Patterns of linkage disequilibrium were established and common haplotypes estimated.</p> <p>Results</p> <p>Fifteen variants were identified in these genes, seven of which are novel, and putatively functional SNPs were subsequently genotyped using TaqMan™, Invader™ or Pyrosequencing^®technology. No significant differences (<it>p </it>> 0.1) were found in genotype or allele distributions between cases and controls for any of the SNPs assessed.</p> <p>Conclusion</p> <p>Our results suggest common variants in <it>TGFB1</it>, <it>TGFBR1 </it>and <it>TGFBR2 </it>genes do not strongly influence genetic susceptibility to diabetic nephropathy in an Irish Caucasian population.</p>