Evaluation of <it>DOK5 </it>as a susceptibility gene for type 2 diabetes and obesity in North Indian population

• Main Authors: Tandon Nikhil, Ghosh Saurabh, Dwivedi Om, Chauhan Ganesh, Mahajan Anubha, Tabassum Rubina, Bharadwaj Dwaipayan
• Format: Article
• Language: English
• Published: BMC 2010-02-01
• Series: BMC Medical Genetics
• Online Access: http://www.biomedcentral.com/1471-2350/11/35

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes is a complex metabolic disorder with obesity being a major contributing factor in its development. Susceptibility loci for type 2 diabetes and obesity have been localized on different chromosomal regions by various genome-wide linkage scans. Of these chromosomal regions, 20q13 is one of the strongest linked regions for type 2 diabetes as well as obesity. On 20q13 lies <it>DOK5 </it>that seems to be a strong functional and positional candidate for type 2 diabetes and obesity because of its involvement in insulin signaling and immune responses. Hence, for the first time, we explored <it>DOK5 </it>as a potential type 2 diabetes and obesity susceptibility gene.</p> <p>Methods</p> <p>We sequenced 43 subjects for polymorphisms in functionally relevant regions of <it>DOK5</it>. A total of 10 SNPs that included 5 that were identified by sequencing and 5 additional SNPs from NCBI Variation Database were genotyped in 2,115 participants comprising of 1,073 patients with type 2 diabetes and 1,042 controls of Indo-European ethnicity from North India.</p> <p>Results</p> <p>We identified a novel variant in intron 7 referred to as DK176673. We found nominal association of three SNPs-rs6064099 (OR = 0.75, <it>P </it>= 0.019), rs873079 (OR = 0.76, <it>P </it>= 0.036) and DK176673 (OR = 1.55, <it>P </it>= 0.037) with type 2 diabetes among normal-weight subjects [BMI < 23 kg/m²]. The haplotype GGC harboring rs6068916, rs6064099 and rs873079 showed strong association with type 2 diabetes among normal-weight subjects (OR = 1.37, <it>P</it>/<it>P</it>_perm= 5.8 × 10^-3/0.037). Association analysis with obesity revealed that rs6064099 is associated with reduced susceptibility for obesity (OR = 0.48, <it>P </it>= 6.8 × 10^-3). Also, haplotype GGC conferred increased susceptibility for obesity (OR = 1.27, <it>P</it>/<it>P</it>_perm= 9.0 × 10^-3/0.039). Also, rs6064099 was significantly associated with reduced BMI [median(IQR) = 24.0(20.7-27.1) vs 23.9(20.2-26.8) vs 21.8(19.2-24.7) for GG vs GC vs CC, <it>P </it>= 7.0 × 10^-3].</p> <p>Conclusions</p> <p>We identified <it>DOK5 </it>as a novel susceptibility gene for obesity and type 2 diabetes in North Indian subjects. Association of <it>DOK5 </it>variants both with obesity and type 2 diabetes suggests that these variants might modulate type 2 diabetes susceptibility through obesity.</p>