Multi-locus HLA class I and II allele and haplotype associations with follicular lymphoma

被引：26

作者：

Skibola, C. F. ^{[1
]}

Akers, N. K. ^{[1
]}

Conde, L. ^{[1
]}

Ladner, M. ^{[2
]}

Hawbecker, S. K. ^{[2
]}

Cohen, F. ^{[2
]}

Ribas, F. ^{[2
]}

Erlich, H. A. ^{[2
,3
]}

Goodridge, D. ^{[4
]}

Trachtenberg, E. A. ^{[2
]}

Smith, M. T. ^{[1
]}

Bracci, P. M. ^{[5
]}

机构：

[1] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA

[2] Childrens Hosp Oakland Res Inst, Ctr Genet, Oakland, CA USA

[3] Conexio Genom, Perth, WA, Australia

[4] Roche Mol Syst, Alameda, CA USA

[5] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

来源：

TISSUE ANTIGENS | 2012年 / 79卷 / 04期

基金：

美国国家卫生研究院;

关键词：

follicular lymphoma; genetic risk factors; human leukocyte antigen; next-generation sequencing; HIGH-RESOLUTION; HODGKINS-DISEASE; SUSCEPTIBILITY; EXPRESSION; SURVIVAL; REGION;

D O I：

10.1111/j.1399-0039.2012.01845.x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Follicular lymphoma (FL) is an indolent, sometimes, fatal disease characterized by recurrence at progressively shorter intervals and is frequently refractive to therapy. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region on chromosome 6p21.32-33 that are statistically significantly associated with FL risk. Low to medium resolution typing of single or multiple HLA genes has provided an incomplete picture of the total genetic risk imparted by this highly variable region. To gain further insight into the role of HLA alleles in lymphomagenesis and to investigate the independence of validated SNPs and HLA alleles with FL risk, high-resolution HLA typing was conducted using next-generation sequencing in 222 non-Hispanic White FL cases and 220 matched controls from a larger San Francisco Bay Area population-based casecontrol study of lymphoma. A novel protective association was found between the DPB1*03:01 allele and FL risk [odds ratio (OR) = 0.39, 95% confidence interval (CI) = 0.210.68]. Extended haplotypes DRB1*01:01-DQA1*01:01-DQB1*05:01 (OR = 2.01, 95% CI = 1.223.38) and DRB1*15-DQA1*01-DQB1*06 (OR = 0.55, 95% CI = 0.360.82) also influenced FL risk. Moreover, DRB1*15-DQA1*01-DQB1*06 was highly correlated with an established FL risk locus, rs2647012. These results provide further insight into the critical roles of HLA alleles and SNPs in FL pathogenesis that involve multi-locus effects across the HLA region.

引用

页码：279 / 286

页数：8

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