Genome-wide association study of hepatitis C virus- and cryoglobulin-related vasculitis

被引：51

作者：

Zignego, A. L. ^{[1
]}

Wojcik, G. L. ^{[2
]}

Cacoub, P. ^{[3
,4
,5
,6
,7
]}

Visentini, M. ^{[8
]}

Casato, M. ^{[8
]}

Mangia, A. ^{[9
]}

Latanich, R. ^{[10
]}

Charles, E. D. ^{[11
]}

Gragnani, L. ^{[1
]}

Terrier, B. ^{[3
,4
]}

Piazzole, V. ^{[9
]}

Dustin, L. B.

Khakoon, S. I. ^{[12
]}

Busch, M. P. ^{[13
]}

Lauer, G. M. ^{[14
]}

Kim, A. Y. ^{[14
]}

Alric, L. ^{[15
]}

Thomas, D. L. ^{[10
]}

Duggal, P. ^{[2
]}

机构：

[1] Univ Florence, Florence, Italy

[2] Johns Hopkins Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA

[3] Sorbonne Univ, Univ Paris 06, UMR 7211, Paris, France

[4] Sorbonne Univ, Univ Paris 06, Inflammat Immunopathol Biotherapy Dept DHU i2B, Paris, France

[5] INSERM, UMR S 959, Paris, France

[6] CNRS, FRE3632, Paris, France

[7] Grp Hosp Pitie Salpetriere, AP HP, Dept Internal Med & Clin Immunol, F-75634 Paris, France

[8] Univ Rome, Rome, Italy

[9] Casa Sollievo della Sofferenza Hosp, Liver Unit, San Giovanni Rotondo, Italy

[10] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA

[11] Rockefeller Univ, New York, NY 10021 USA

[12] Univ Southampton, Southampton, Hants, England

[13] Blood Syst Res Inst, San Francisco, CA USA

[14] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA

[15] Univ Toulouse 3, CHU Purpan Hosp, F-31062 Toulouse, France

来源：

GENES AND IMMUNITY | 2014年 / 15卷 / 07期

基金：

美国国家卫生研究院; 英国惠康基金;

关键词：

MIXED CRYOGLOBULINEMIA; IMPUTATION; RISK; SUSCEPTIBILITY; PREVALENCE; INFECTION; REGION; CELLS;

D O I：

10.1038/gene.2014.41

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The host genetic basis of mixed cryoglobulin vasculitis is not well understood and has not been studied in large cohorts. A genome-wide association study was conducted among 356 hepatitis C virus (HCV) RNA-positive individuals with cryoglobulin-related vasculitis and 447 ethnically matched, HCV RNA-positive controls. All cases had both serum cryoglobulins and a vasculitis syndrome. A total of 899 641 markers from the Illunnina HumanOmni1-Quad chip were analyzed using logistic regression adjusted for sex, as well as genetically determined ancestry. Replication of select single-nucleotide polymorphisms (SNPs) was conducted using 91 cases and 180 controls, adjusting for sex and country of origin. The most significant associations were identified on chromosome 6 near the NOTCH4 and MHC class II genes. A genome-wide significant association was detected on chromosome 6 at SNP rs9461776 (odds ratio = 2.16, P= 1.16E - 07) between HLA-DRB1 and DQA1: this association was further replicated in additional independent samples (meta-analysis P=7.1 x 10(-9)). A genome-wide significant association with cryoglobulin-related vasculitis was identified with SNPs near NOTCH4 and MHC Class II genes. The two regions are correlated and it is difficult to disentangle which gene is responsible for the association with mixed cryoglobulinemia vasculitis in this extended major histocompatibility complex region.

引用

页码：500 / 505

页数：6

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