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

Yuka Yamaguchi¹ , Maki Moritani¹ , Toshihito Tanahashi¹ , Dai Osabe² , Kyoko Nomura² , Yuka Fujita¹ , Parvaneh Keshavarz¹ , Kiyoshi Kunika¹ , Naoto Nakamura³ , Toshikazu Yoshikawa³ , Eiichiro Ichiishi⁴ , Hiroshi Shiota⁵ , Natsuo Yasui⁶ , Hiroshi Inoue¹ and Mitsuo Itakura¹

¹Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan

²Department of Bioinformatics, Division of Life Science Systems, Fujitsu Limited, 1-5-2, Higashishinbashi, Minato-ku, Tokyo, 105-7123, Japan

³Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465, Kajii-cho, Hirokoji-Kawaramachi, Kamigyo-ku, Kyoto, 602-8566, Japan

⁴New Industry Creation Hatchery Center, Tohoku University, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8579, Japan

⁵Department of Ophthalmology and Visual Neuroscience, Institute of Health Bioscience, The University of Tokushima, 770-8503, Japan

⁶Department of Orthopedics, Institute of Health Biosciences, The University of Tokushima, 770-8503, Japan

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BMC Medical Genetics 2008, 9:22doi:10.1186/1471-2350-9-22


Published:	27 March 2008

Abstract

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.