Association between LEP and LEPR gene polymorphisms and dyslipidemia in patients using atypical antipsychotic medication.

BACKGROUND: Treatment with atypical antipsychotic agents is often complicated by dyslipidemia, which is a risk factor for cardiovascular disease.

OBJECTIVES: To determine whether the LEPR Q223R, the LEP -2548G/A, and the HTR2C -759C/T polymorphisms are associated with dyslipidemia in patients using atypical antipsychotic drugs.

METHODS: A cross-sectional study design was used. The study population included all patients who had been screened for dyslipidemia between January 2008 and March 2009 and had been using an atypical antipsychotic for at least 3 months at the moment of screening. Primary outcome measure was the mean total cholesterol (TC)/HDL ratio. Determinants were the LEPR Q223R (rs1137101), the LEP -2548G/A SNP (rs7799039), and the HTR2C -759C/T (rs3813929) polymorphisms.

RESULTS: A total of 353 patients was included in the study, of which 184 (52.1%) were men and 169 (47.9%) were women. Overall, no significant differences were found between the different genotype groups. However, in patients with a first admission to the hospital less than a year ago, the LEP -2548G allele had a lower mean TC/HDL ratio compared with patients without the LEP -2548G allele (6.41 vs. 4.12, P-adj: 0.017) and patients with the LEPR 223R allele had a lower mean TC/HDL ratio compared with patients without the LEPR 223R allele (5.04 vs. 3.92, P-adj: 0.019). The association between the LEP -2548G/A allele and the TC/HDL ratio in recent patients was present only in men.

CONCLUSION: Genetic variation in the LEP and LEPR gene may be associated with short-term dyslipidemia in patients using atypical antipsychotic agents.