Association between Functional CYP2D6 Polymorphisms and Susceptibility to Autoimmune Diseases: A Meta-Analysis

ABSTRACT

Objective: This study aimed to explore whether functional CYP2D6 polymorphisms are associated with susceptibility to autoimmune diseases.

Methods: A meta-analysis was conducted on associations between autoimmune diseases and functional CYP2D6*4 1934 A/G and *3 polymorphisms and CYP2D6 phenotypes.

Results: Twelve studies with 1,472 patients and 3,328 controls were included. Autoimmune disease and the CYP2D6 1934 A allele were significantly associated in the overall group, consistent with the Hardy–Weinberg equilibrium (OR = 1.227, 95% CI = 1.071–1.406, p = 0.003); stratification by ethnicity indicated that the CYP2D6 1934 A allele and autoimmune diseases were associated in Caucasians (OR = 1.225, 95% CI = 1.010–1.485, p = 0.039). The CYP2D6*3 allele was also associated with autoimmune diseases in Caucasians (OR = 1.977, 95% CI = 1.125–3.472, p = 0.018). Stratified by autoimmune disease type revealed that the CYP2D6 1934 AA genotype was associated with systemic lupus erythematosus (SLE; OR = 2.007, 95% CI = 1.170–3.442, p = 0.011) and ankylosing spondylitis (AS; OR = 2.317, 95% CI = 1.422–3.774, p = 0.001). The CYP2D6 PM+IM phenotype was significantly associated with autoimmune diseases in Caucasians (OR = 1.526, 95% CI = 1.038–2.246, p = 0.032) and with SLE (OR = 1.778, 95% CI = 1.249–2.532, p = 0.001).

Conclusions: This meta-analysis indicates that CYP2D6*4 and *3 polymorphisms and the CYP2D6 phenotype are associated with susceptibility to autoimmune diseases in Caucasians; particularly, the CYP2D6*4 polymorphism and CYP2D6 PM+IM phenotype are risk factors for SLE development.

KEYWORDS:

• Autoimmune diseases
• CYP2D6
• meta-analysis
• polymorphism

Disclosure statement

The authors have no conflict of interest to declare.

Funding

This study was supported in part by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea [grant number HI15C2958].

Additional information

Funding

This study was supported in part by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea [grant number HI15C2958].