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J Am Soc Nephrol. 2017 Nov;28(11):3383-3394. doi: 10.1681/ASN.2016121331. Epub 2017 Jul 28.

Association Analysis of the MHC in Lupus Nephritis.

Xu R1,2, Li Q3, Liu R1,4, Shen J3, Li M1, Zhao M5, Wang M1, Liao Q3, Mao H1, Li Z1, Zhou N3, Yin P1, Li Y3, Tang X1, Wu T3, Zhong Z1, Wang Y3, Ai Z1, Wang O3, Chen N6, Yang X3, Fang J3, Fu P7, Gu J8, Ye K9, Chen J10, Dai L11, Liu H12, Liu Z13, Liao Y14, Wan J15, Ding G16, Zhao J17, Zhang H18, Fu S19, Sun L20,21, Zhang X21,22, Yang H3,23, Wang J3,23, Wang J3,24,20, Liu J20,25,26, Li Y27, Yu X28,12.

Author information

1
Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Key Laboratory of Nephrology, Ministry of Health, Guangzhou, Guangdong, China.
2
Department of Nephrology, Shenzhen Second People's Hospital and the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
3
BGI Genomics, BGI-Shenzhen, Shenzhen, China.
4
Nephrology and Rheumatology Department, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, China.
5
Renal Division, Peking University First Hospital, Peking University, Institute of Nephrology, Beijing, China.
6
Department of Nephrology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
7
Department of Nephrology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
8
Department of Rheumatology, The Third Affiliated Hospital and.
9
Department of Nephrology, The People's Hospital of Guangxi Autonomous Region, Nanning, Guangxi, China.
10
Department of Nephrology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, Fujian, China.
11
Department of Rheumatology and Clinical Immunology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
12
Institute of Nephrology, Guangdong Medical University, Zhanjiang, Guangdong, China.
13
Department of Nephrology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China.
14
Department of Nephrology, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China.
15
Department of Nephrology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
16
Department of Nephrology, Renmin Hospital, Wuhan University, Wuhan, Hubei, China.
17
Department of Nephrology, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
18
Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
19
Department of Nephrology, The Second Hospital, Hebei Medical University, Shijiazhuang, Hebei, China.
20
Institute of Dermatology and Department of Dermatology, No. 1 Hospital and.
21
Collaborative Innovation Center of Complex and Severe Skin Disease, Anhui Medical University, Hefei, Anhui, China.
22
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
23
James D. Watson Institute of Genome Sciences, Hangzhou, China.
24
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
25
Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; and.
26
School of Biological Sciences, Anhui Medical University, Hefei, Anhui, China.
27
BGI Genomics, BGI-Shenzhen, Shenzhen, China; liyr@icarbonx.com yuxq@mail.sysu.edu.cn.
28
Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Key Laboratory of Nephrology, Ministry of Health, Guangzhou, Guangdong, China; liyr@icarbonx.com yuxq@mail.sysu.edu.cn.

Abstract

Lupus nephritis (LN) is one of the most prevalent and serious complications of SLE, with significant effects on patient and renal survival. Although a large number of genetic variants associated with SLE have been identified, biomarkers that correlate with LN are extremely limited. In this study, we performed a comprehensive sequencing analysis of the whole MHC region in 1331 patients with LN and 1296 healthy controls and validated the independent associations in another 950 patients with LN and 1000 controls. We discovered five independent risk variants for LN within the MHC region, including HLA-DRβ1 amino acid 11 (Pomnibus<0.001), HLA-DQβ1 amino acid 45 (P<0.001; odds ratio, 0.58; 95% confidence interval, 0.52 to 0.65), HLA-A amino acid 156 (Pomnibus<0.001), HLA-DPβ1 amino acid 76 (Pomnibus<0.001), and a missense variant in PRRC2A (rs114580964; P<0.001; odds ratio, 0.38; 95% confidence interval, 0.30 to 0.49) at genome-wide significance. These data implicate aberrant peptide presentation by MHC classes 1 and 2 molecules and sex hormone modulation in the development of LN.

KEYWORDS:

Deep Sequencing; Major Histocompatibility Complex; Multiple Risk Variants; lupus nephritis

PMID:
28754791
PMCID:
PMC5661284
DOI:
10.1681/ASN.2016121331
[Indexed for MEDLINE]
Free PMC Article

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