Abstract
BackgroundChromosome 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 D15S118 and D15S117 in a Japanese population using a region-wide case-control association test.MethodsA 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.ResultsSNP2140 (rs2412747) (C/T) in intron 33 of the ubiquitin protein ligase E3 component n-recognin 1 (UBR1) gene was selected as a landmark SNP based on repeated significant associations in Stage 1 and Stage 2. However, the marginal p value (p = 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.ConclusionThe 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.
Highlights
Chromosome 15q14-22.1 has been linked to type 2 diabetes (T2D) and its related traits in Japanese and other populations
Adipose, and liver tissues and impaired insulin secretion from pancreatic β cells contribute to the pathogenesis of type 2 diabetes (T2D) [1]
Because candidate regions supported by replicated linkage signals in Japanese and other populations are expected to map T2D susceptibility gene(s), a region-wide association test was used as an alternative affective approach with the availability of unbiased reliability, timeliness and cost efficiency
Summary
Chromosome 15q14-22.1 has been linked to type 2 diabetes (T2D) and its related traits in Japanese and other populations. The assessment in Japanese T2D patients, who characteristically have a lower body mass index (BMI) and a lower fasting insulin level than Caucasians [9], has not been largely performed These differences suggest that Japanese individuals with T2D might have a different genetic background from other populations, and susceptibility variant(s) or gene(s) for the development of T2D in Japanese can only be identified with genetic assessment. In three studies of genome-wide linkage scan of Japanese subjects [11,12,13], chromosome 15q14-22.1 showed significant evidence of linkage with T2D (LOD = 2.41) [12] and a maximum LOD score (MLS) of 3.91 for early onset T2D [11] (Table 1) This region overlaps candidate region found in other populations, including Mexican Americans [14] and Pima Indians [15], findings that were replicated in a subsequent study of Mexican Americans [16] (Table 1). We focused on chromosome 15q14-22.1 at 32.6–51.2 cM as the susceptibility region in Japanese
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