A genome-wide association study identifies ITGA9 conferring risk of nasopharyngeal carcinoma

被引：74

作者：

Ng, Ching Ching ^{[2
,3
]}

Yew, Poh Yin ^{[2
,3
]}

Puah, Suat Moi ^{[2
,3
]}

Krishnan, Gopala ^{[8
]}

Yap, Lee Fah ^{[9
]}

Teo, Soo Hwang ^{[9
]}

Lim, Paul Vey Hong ^{[10
]}

Govindaraju, Selvaratnam ^{[11
]}

Ratnavelu, Kananathan ^{[11
]}

Sam, Choon Kook ^{[4
]}

Takahashi, Atsushi ^{[5
]}

Kubo, Michiaki ^{[7
]}

Kamatani, Naoyuki ^{[5
]}

Nakamura, Yusuke ^{[1
,2
]}

Mushiroda, Taisei ^{[6
]}

机构：

[1] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab,Minato Ku, Tokyo 1088639, Japan

[2] RIKEN Ctr Genom Med, Lab Int Alliance, Tsurumi Ku, Yokohama, Kanagawa, Japan

[3] Univ Malaya, Fac Sci, Inst Biol Sci, Kuala Lumpur 50603, Malaysia

[4] Nanyang Technol Univ, Natl Inst Educ, Singapore, Singapore

[5] RIKEN Ctr Genom Med, Lab Stat Anal, Minato Ku, Tokyo, Japan

[6] RIKEN Ctr Genom Med, Lab Pharmacogenet, Tsurumi Ku, Yokohama, Kanagawa, Japan

[7] RIKEN Ctr Genom Med, Lab Genotyping Dev, Tsurumi Ku, Yokohama, Kanagawa, Japan

[8] Univ Malaya, Fac Med, Dept Otorhinolaryngol, Kuala Lumpur 50603, Malaysia

[9] Canc Res Initiat Fdn, Sime Darby Med Ctr, Selangor, Malaysia

[10] Tung Shin Hosp, Kuala Lumpur, Malaysia

[11] NCI Canc Hosp, Negeri Sembilan, Malaysia

来源：

JOURNAL OF HUMAN GENETICS | 2009年 / 54卷 / 07期

关键词：

genome-wide association study; GWAS; integrin-alpha; 9; ITGA9; nasopharyngeal carcinoma; NPC; SNP; GENETIC POLYMORPHISMS; VIRUS RECEPTOR; SUSCEPTIBILITY; CHINESE; INTEGRINS; ETIOLOGY; XRCC1;

D O I：

10.1038/jhg.2009.49

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

To identify a gene(s) susceptible to nasopharyngeal carcinoma (NPC), we carried out a genome-wide association study (GWAS) through genotyping of more than 500 000 tag single-nucleotide polymorphisms (SNPs), using an initial sample set of 111 unrelated NPC patients and 260 controls of a Malaysian Chinese population. We further evaluated the top 200 SNPs showing the smallest P-values, using a replication sample set that consisted of 168 cases and 252 controls. The combined analysis of the two sets of samples found an SNP in intron 3 of the ITGA9 (integrin-alpha 9) gene, rs2212020, to be strongly associated with NPC (P = 8.27 x 10(-7), odds ratio (OR) = 2.24, 95% confidence intervals (CI) = 1.59-3.15). The gene is located at 3p21 which is commonly deleted in NPC cells. We subsequently genotyped additional 19 tag SNPs within a 40-kb linkage disequilibrium (LD) block surrounding this landmark SNP. Among them, SNP rs189897 showed the strongest association with a P-value of 6.85 x 10(-8) (OR = 3.18, 95% CI = 1.94-5.21), suggesting that a genetic variation(s) in ITGA9 may influence susceptibility to NPC in the Malaysian Chinese population. Journal of Human Genetics (2009) 54, 392-397; doi: 10.1038/jhg.2009.49; published online 29 May 2009

引用

页码：392 / 397

页数：6

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