Metadata of CSIR Papers
View Archive Info| Field | Value | |
| Creator |
Tabassum, R
Mahajan, A Chauhan, G Dwivedi, OP Ghosh, S Tandon, N Bharadwaj, D |
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| Subject |
Genetics & Heredity
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| Description |
Background: 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 DOK5 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 DOK5 as a potential type 2 diabetes and obesity susceptibility gene. Methods: We sequenced 43 subjects for polymorphisms in functionally relevant regions of DOK5. 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. Results: We identified a novel variant in intron 7 referred to as DK176673. We found nominal association of three SNPs-rs6064099 (OR = 0.75, P = 0.019), rs873079 (OR = 0.76, P = 0.036) and DK176673 (OR = 1.55, P = 0.037) with type 2 diabetes among normal-weight subjects [BMI < 23 kg/m(2)]. The haplotype GGC harboring rs6068916, rs6064099 and rs873079 showed strong association with type 2 diabetes among normal-weight subjects (OR = 1.37, P/P(perm) = 5.8 x 10(-3)/0.037). Association analysis with obesity revealed that rs6064099 is associated with reduced susceptibility for obesity (OR = 0.48, P = 6.8 x 10(-3)). Also, haplotype GGC conferred increased susceptibility for obesity (OR = 1.27, P/P(perm) = 9.0 x 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, P = 7.0 x 10(-3)]. Conclusions: We identified DOK5 as a novel susceptibility gene for obesity and type 2 diabetes in North Indian subjects. Association of DOK5 variants both with obesity and type 2 diabetes suggests that these variants might modulate type 2 diabetes susceptibility through obesity.
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| Publisher |
BIOMED CENTRAL LTDLONDON236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
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| Date |
2011-09-20T12:07:11Z
2011-09-20T12:07:11Z 2010 |
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| Type |
Article
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| Identifier |
BMC MEDICAL GENETICS
1471-2350 http://hdl.handle.net/123456789/13141 |
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| Language |
English
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