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Published on: July 15, 2011
LEPR gene polymorphisms and pneumonia risk in Taiwanese schizophrenia patients under clozapine treatment
Hui-Ching Huang1, Bo-Jian Wu2, Chuan-Hsun Yu2
1Department of Pharmacy, Yuli Hospital, Ministry of Health and Welfare, Taiwan; Department of Pharmacology, School of Medicine, Tzu Chi University, Hualien, Taiwan.
Background:
Clozapine, the preferred medication for treatment-resistant schizophrenia, elevates leptin and pro-inflammatory cytokine levels in patients' blood. Inhibition of the clozapine metabolic enzyme CYP1A2 can potentially lead to toxicity and pneumonia. Leptin has a pro-inflammatory effect on the immune system. This study explores whether polymorphisms in the leptin (LEP) and leptin receptor (LEPR) genes are associated with increased risk of clozapine-induced pneumonia.
Methods:
A retrospective cohort study was conducted with 302 consecutive schizophrenia patients who had been on clozapine for at least 6 months. Blood samples were collected to identify genetic polymorphisms in the LEP and LEPR genes, and the association between these polymorphisms and pneumonia incidence was analyzed using Cox proportional hazards models.
Results:
Among the SNPs in the LEPR gene, individuals with the A/A genotype of rs1137101 had a 14.96-fold higher pneumonia risk than those with the G/G genotype (p = 0.001). Carriers of the G/G genotype of rs1805096 had a 3.72-fold increased risk compared to those with A/A (p = 0.033). For rs6657868, the A/G and G/G genotypes were associated with 2.23-fold (p = 0.005) and 6.73-fold (p = 0.013) higher risks, respectively, compared to the A/A genotype. Similarly, for rs9436746, the A/C and C/C genotypes had 2.25-fold (p = 0.005) and 5.37-fold (p = 0.029) increased risks, respectively, compared to A/A.
Conclusion:
LEPR polymorphisms associated with an increased risk of pneumonia in Taiwanese schizophrenia patients treated with clozapine.
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