Association between complement 4 copy number variation and systemic lupus erythematosus: a meta-analysis.

Area of Science:

• Genetics
• Immunology
• Autoimmune Diseases

Background:

• Systemic lupus erythematosus (SLE) is a complex autoimmune disease influenced by multiple genetic factors.
• Complement 4 (C4) copy number variation (CNV) on chromosome 6 is implicated, with low C4 levels associated with SLE activity.
• C4 gene encodes C4A and C4B paralogs, crucial components of the immune system.

Purpose of the Study:

• To conduct a meta-analysis to comprehensively evaluate the role of C4 copy number variation (CNV) in systemic lupus erythematosus (SLE).
• To investigate the association between C4 CNV and SLE across different populations and C4 paralogs.

Main Methods:

• Systematic literature search of PubMed, Embase, and Web of Science databases.
• Inclusion of eight case-control studies (4107 SLE patients, 5889 controls) with data extracted independently.
• Genotyping methods included TaqMan real-time PCR, paralog ratio test, and multiplex ligation-dependent probe amplification (MLPA).

Main Results:

• Lower total C4 CNV and C4A CNV were significantly associated with SLE (pooled ORs: 1.55 and 1.86, respectively).
• Subgroup analysis revealed a strong association between total C4 CNV and lower C4A CNV with SLE in Caucasians (pooled ORs: 1.84 and 2.23, respectively).
• No significant association was found in East Asians, nor with C4B CNV, long C4 CNV, or short C4 CNV.

Conclusions:

• The meta-analysis confirms that reduced total C4 CNV and C4A CNV are associated with SLE, particularly in Caucasian populations.
• C4 CNV, especially C4A, may serve as a genetic biomarker for SLE risk and activity in certain ethnic groups.
• Further research is recommended to explore the C4 gene-SLE relationship in diverse ethnic groups.