Genetic Variants That Are Associated with Neuropsychiatric Systemic Lupus Erythematosus.

Roger C Ho, Huiyi Ong, Chandra Thiaghu, Yanxia Lu, Cyrus S Ho, Melvyn W Zhang

Journal: The Journal of rheumatology 2016;43(3):541-51

PMID: 26773105

Abstract

OBJECTIVE

While genetic risks have been implicated in systemic lupus erythematosus (SLE), the involvement of various genotypes in neuropsychiatric SLE (NPSLE) remains uncertain. The present metaanalysis aimed to combine data from different studies and evaluate the association between each genotype and the risk of developing NPSLE.

METHODS

Studies were searched and retrieved from online databases (PubMed, EMBASE, BIOSIS, and ScienceDirect). Case-control studies were chosen if they reported genotype frequencies of the γ Fc region (FCγR) receptors II-A, III-A, and III-B; tumor necrosis factor-α (TNF-α); mannan-binding lectin (MBL); integrin alpha M (ITGAM); interleukin (IL) 1, IL-1β, and IL-6; IL-10 promoter; and vitamin D genes. The OR were used to assess the strength of this association between patients with NPSLE and SLE.

RESULTS

A total of 33 studies were considered in this metaanalysis. The results suggest that these genotypes demonstrated a significant association with NPSLE: the homozygous FCγR IIIa 158 FF genotype (OR 1.89, p = 0.03 for FF vs VV + FV), heterozygous FCγR IIIb NA1/2 genotype (OR 2.14, p = 0.03 for NA1/2 vs NA1/1; OR 1.81, p = 0.04 for NA1/2 vs NA1/1 + NA2/2), and homozygous ITGAM rs1143679 HH genotype (OR 3.39, p = 0.04 for HH vs RH; OR 3.11, p = 0.048 for HH vs RR + RH). Polymorphisms of the TNF-α, MBL2, IL-1, IL-1β, IL-6, IL-10 promoter, and vitamin D receptor genes did not show a statistically significant association with the risk of developing NPSLE (p > 0.05).

CONCLUSION

This metaanalysis indicates that polymorphisms in the pathways of immune complex clearance, such as the FcγRIIIa, FcγRIIIb, and ITGAM genotypes, are potential susceptibility genes for NPSLE.

Address: From the Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore; Institute of Mental Health, Singapore; Department of Clinical Psychology and Psychiatry/School of Public Health, Zhejiang University College of Medicine, Hangzhou, China.R.C. Ho, FRCPC, Assistant Professor, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore; H. Ong, MBBS, Medical Officer, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore; C. Thiaghu, MBBS, Medical Officer, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore; Y. Lu, PhD, Assistant Professor, Department of Clinical Psychology and Psychiatry/School of Public Health, Zhejiang University College of Medicine; C.S. Ho, MRCPsych, Specialist Registrar, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore; M.W. Zhang, MRCPsych, Specialist Registrar, Institute of Mental Health.; From the Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore; Institute of Mental Health, Singapore; Department of Clinical Psychology and Psychiatry/School of Public Health, Zhejiang University College of Medicine, Hangzhou, China.R.C. Ho, FRCPC, Assistant Professor, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore; H. Ong, MBBS, Medical Officer, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore; C. Thiaghu, MBBS, Medical Officer, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore; Y. Lu, PhD, Assistant Professor, Department of Clinical Psychology and Psychiatry/School of Public Health, Zhejiang University College of Medicine; C.S. Ho, MRCPsych, Specialist Registrar, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore; M.W. Zhang, MRCPsych, Specialist Registrar, Institute of Mental Health. [email protected].

DOI: 10.3899/jrheum.150884