Lack of association of genetic variation in chromosome region 15q14-22.1 with type 2 diabetes in a Japanese population

<p>Abstract</p> <p>Background</p> <p>Chromosome 15q14-22.1 has been linked to type 2 diabetes (T2D) and its related traits in Japanese and other populations. The presence of T2D disease susceptibility variant(s) was assessed in the 21.8 Mb region between <it>D15S118 </it>and <it>D15S117 </it>in a Japanese population using a region-wide case-control association test.</p> <p>Methods</p> <p>A two-stage association test was performed using Japanese subjects: The discovery panel (Stage 1) used 372 cases and 360 controls, while an independent replication panel (Stage 2) used 532 cases and 530 controls. A total of 1,317 evenly-spaced, common SNP markers with minor allele frequencies > 0.10 were typed for each stage. Captured genetic variation was examined in HapMap JPT SNPs, and a haplotype-based association test was performed.</p> <p>Results</p> <p>SNP2140 (rs2412747) (<it>C/T</it>) in intron 33 of the ubiquitin protein ligase E3 component n-recognin 1 (<it>UBR1</it>) gene was selected as a landmark SNP based on repeated significant associations in Stage 1 and Stage 2. However, the marginal <it>p </it>value (<it>p </it>= 0.0043 in the allelic test, OR = 1.26, 95% CI = 1.07–1.48 for combined samples) was weak in a single locus or haplotype-based association test. We failed to find any significant SNPs after correcting for multiple testing.</p> <p>Conclusion</p> <p>The two-stage association test did not reveal a strong association between T2D and any common variants on chromosome 15q14-22.1 in 1,794 Japanese subjects. A further association test with a larger sample size and denser SNP markers is required to confirm these observations.</p