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

• Published in: BMC medical genetics Vol. 9; no. 1; p. 22
• Main Authors: Yamaguchi, Yuka, Moritani, Maki, Tanahashi, Toshihito, Osabe, Dai, Nomura, Kyoko, Fujita, Yuka, Keshavarz, Parvaneh, Kunika, Kiyoshi, Nakamura, Naoto, Yoshikawa, Toshikazu, Ichiishi, Eiichiro, Shiota, Hiroshi, Yasui, Natsuo, Inoue, Hiroshi, Itakura, Mitsuo
• Format: Journal Article
• Language: English
• Published: London BioMed Central 27.03.2008; BioMed Central Ltd; BMC
• Subjects: Adult; Aged; Biological markers; Biomedical and Life Sciences; Biomedicine; Case-Control Studies; Chromosome Mapping; Chromosomes, Human, Pair 15; Cytogenetics; Diabetes Mellitus, Type 2 - genetics; Female; Gene Function; Genetic aspects; Genetic Variation; Haplotypes; Health aspects; Human Genetics; Humans; Japan; Linkage Disequilibrium; Male; Middle Aged; Polymorphism, Single Nucleotide; Research Article; Risk factors; Type 2 diabetes; Japan; Association Test; Allelic Test; Exocrine Pancreatic Insufficiency; Linkage Disequilibrium Block; Japanese Subject
• ISSN: 1471-2350; 1471-2350
• DOI: 10.1186/1471-2350-9-22

Background 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 D15S118 and D15S117 in a Japanese population using a region-wide case-control association test. Methods 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. Results SNP2140 (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. Conclusion 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.