title: Impact of genetic factors on dyslipidemia in HIV-infected patients starting antiretroviral therapy.
abstract: OBJECTIVE
  The impact of host genetic factors on the incidence of dyslipidemia in antiretroviral-naive HIV patients starting antiretroviral therapy (ART) is not clear. We assessed the role of single nucleotide polymorphisms (SNPs) identified from previous genome-wide association studies adjusting for the contribution of nongenetic factors.
  
  
  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.
  
  
  CONCLUSIONS
  In HIV-infected patients staring ART, one SNP in APOB was associated with an increase of LDL-C. SNPs in ABCA1/LIPC/CETP were favourably associated with HDL-C when ART included NNRTI. However, an unfavourable effect on T-Chol and triglyceride levels was observed when ART included protease inhibitor. The risk of hypercholesterolaemia increased with age and decreased with HCV coinfection. These findings might help to individualize the selection of ART.
authors.affiliation: University of Barcelona, Barcelona, Spain.
authors.forename: Lander
authors.initials: L
authors.lastname: Egaña-Gorroño
authors.forename: Esteban
authors.initials: E
authors.lastname: Martínez
authors.forename: Bru
authors.initials: B
authors.lastname: Cormand
authors.forename: Tuixent
authors.initials: T
authors.lastname: Escribà
authors.forename: Jose
authors.initials: J
authors.lastname: Gatell
authors.forename: Mireia
authors.initials: M
authors.lastname: Arnedo
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D060085:Coinfection / Q000097:blood / Q000188:drug therapy; D004334:Drug Administration Schedule; D050171:Dyslipidemias / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D005215:Fasting; D005260:Female; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study; D005838:Genotype; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006679:HIV Seropositivity / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D006526:Hepatitis C / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013030:Spain / Q000453:epidemiology; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D017320:HIV Protease Inhibitors; D008055:Lipids; D018894:Reverse Transcriptase Inhibitors; D014280:Triglycerides