日本人群中15号染色体区域15q14 - 22.1的基因变异与2型糖尿病无关联。

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

作者信息

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

机构信息

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

出版信息

BMC Med Genet. 2008 Mar 27;9:22. doi: 10.1186/1471-2350-9-22.

DOI:10.1186/1471-2350-9-22

PMID:18366806

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2324080/

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.

摘要

背景

在日本及其他人群中，15号染色体的15q14 - 22.1区域已被证实与2型糖尿病（T2D）及其相关性状有关。本研究在日本人群中，通过全区域病例对照关联试验，评估了位于D15S118和D15S117之间21.8 Mb区域内是否存在T2D疾病易感性变异。

方法

采用日本受试者进行两阶段关联试验：发现阶段（第一阶段）使用372例病例和360例对照，独立验证阶段（第二阶段）使用532例病例和530例对照。每个阶段均对1317个均匀分布、次要等位基因频率>0.10的常见单核苷酸多态性（SNP）标记进行基因分型。在国际人类基因组单体型图计划（HapMap）的日本人群（JPT）SNP中检查捕获的遗传变异，并进行基于单倍型的关联试验。

结果

基于在第一阶段和第二阶段反复出现的显著关联，泛素蛋白连接酶E3组分n - 识别蛋白1（UBR1）基因第33内含子中的SNP2140（rs2412747）（C/T）被选为标志性SNP。然而，在单基因座或基于单倍型的关联试验中，其边际p值（等位基因试验中p = 0.0043，合并样本的比值比（OR）= 1.26，95%置信区间（CI）= 1.07 - 1.48）较弱。在进行多重检验校正后，未发现任何显著的SNP。