Chromosome 7p linkage and association study for diabetes related traits and type 2 diabetes in an African-American population enriched for nephropathy

• Main Authors: Gallagher Carla J (Author), Keene Keith L (Author), Langefeld Carl D (Author), Leak Tennille S (Author), Lu Lingyi (Author), Mychaleckyj Josyf C (Author), Rich Stephen S (Author), Freedman Barry I (Author), Bowden Donald W (Author), Sale Michèle M (Author)
• Format: Book
• Published: BMC, 2010-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/1471-2350-11-22; 1471-2350
• Keywords: Internal medicine; RC31-1245; Genetics; QH426-470
• Source: BMC Medical Genetics, Vol 11, Iss 1, p 22 (2010)

<p>Abstract</p> <p>Background</p> <p>Previously we performed a linkage scan of 638 African American affected sibling pairs (ASP) with type 2 diabetes (T2D) enriched for end-stage renal disease (ESRD). Ordered subset linkage analysis (OSA) revealed a linkage peak on chromosome 7p in the subset of families with earlier age of T2D diagnosis.</p> <p>Methods</p> <p>We fine mapped this region by genotyping 11 additional polymorphic markers in the same ASP and investigated a total of 68 single nucleotide polymorphisms (SNPs) in functional candidate genes (<it>GCK1, IL6, IGFBP1 </it>and <it>IGFBP3) </it>for association with age of T2D diagnosis, age of ESRD diagnosis, duration of T2D to onset of ESRD, body mass index (BMI) in African American cases and T2D-ESRD in an African American case-control cohort. OSA of fine mapping markers supported linkage at 28 cM on 7p (near D7S3051) in early-onset T2D families (max. LOD = 3.61, P = 0.002). SNPs in candidate genes and 70 ancestry-informative markers (AIMs) were evaluated in 577 African American T2D-ESRD cases and 596 African American controls.</p> <p>Results</p> <p>The most significant association was observed between ESRD age of diagnosis and SNP rs730497, located in intron 1 of the <it>GCK1 </it>gene (recessive T2D age-adjusted <it>P </it>= 0.0006). Nominal associations were observed with <it>GCK1 </it>SNPs and T2D age of diagnosis (BMI-adjusted <it>P </it>= 0.014 to 0.032). Also, one <it>IGFBP1 </it>and four <it>IGFBP3 </it>SNPs showed nominal genotypic association with T2D-ESRD (<it>P </it>= 0.002-0.049). After correcting for multiple tests, only rs730497 remanined significant.</p> <p>Conclusion</p> <p>Variant rs730947 in the <it>GCK1 </it>gene appears to play a role in early ESRD onset in African Americans.</p>