Impact of genetic factors on dyslipidemia in HIV-infected patients starting antiretroviral therapy.

Methods: We assessed 192 SNPs in an HIV cohort who started ART (1997-2008) including a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor (NNRTI). Patients had fasting plasma lipids, total cholesterol (T-Chol), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides measured prior to their ART initiation and after 1 year. A logistic regression model was constructed and multiple test was corrected using 10% false discovery rate (FDR). Haplotypes and gene interactions were analysed.

Results: A total of 727 individuals were successfully genotyped (n = 381_PI-group; n = 346_NNRTI-group). Age and hepatitis C virus (HCV) coinfection were associated with increases and decreases in T-Chol and LDL-C (P  0.01), respectively. Protease inhibitor containing ART showed an unfavourable association with T-Chol (P  0.01) and triglycerides (P = 7.4E-4) and NNRTI-containing ART was favourably associated with HDL-C (P  0.01). Moreover, SNPs in apolipoprotein B (APOB) were associated with an increase of LDL-C [rs10495712 (P = 3.18E-4); rs754524 (P = 1.26E-3)]. Six SNPs in three genes showed an association with a favourable effect on HDL-C levels when ART included NNRTI: ABCA1 (rs4149313, P = 2.97E-4), LIPC (rs1800588, P = 2.13E-3; rs473224, P = 3.06E-4; rs261336, P = 2.23E-3) and CETP (rs173539, P = 2.96E-3; rs3764261, P = 1.52E-3). After 10% FDR correction for multiple testing, one and six SNPs displayed significant associations with LDL-C and HDL-C, respectively.

Conclusion: A total of 727 individuals were successfully genotyped (n = 381_PI-group; n = 346_NNRTI-group). Age and hepatitis C virus (HCV) coinfection were associated with increases and decreases in T-Chol and LDL-C (P  0.01), respectively. Protease inhibitor containing ART showed an unfavourable association with T-Chol (P  0.01) and triglycerides (P = 7.4E-4) and NNRTI-containing ART was favourably associated with HDL-C (P  0.01). Moreover, SNPs in apolipoprotein B (APOB) were associated with an increase of LDL-C [rs10495712 (P = 3.18E-4); rs754524 (P = 1.26E-3)]. Six SNPs in three genes showed an association with a favourable effect on HDL-C levels when ART included NNRTI: ABCA1 (rs4149313, P = 2.97E-4), LIPC (rs1800588, P = 2.13E-3; rs473224, P = 3.06E-4; rs261336, P = 2.23E-3) and CETP (rs173539, P = 2.96E-3; rs3764261, P = 1.52E-3). After 10% FDR correction for multiple testing, one and six SNPs displayed significant associations with LDL-C and HDL-C, respectively.