title: Polymorphisms in LPL, CETP, and HL protect HIV-infected patients from atherogenic dyslipidemia in an allele-dose-dependent manner.
abstract: HIV-infected patients treated with highly active antiretroviral therapy (HAART) may be predisposed to a lipid profile, associated with increased cardiovascular risk, derived from having high triglycerides (TG) and low high-density lipoprotein cholesterol (HDLc) levels. We propose that genetic variability leaves some HIV-infected patients more predisposed to this lipid profile than others. We performed a cross-sectional, observational study including 321 antiretroviral-treated HIV-infected patients classified as normolipidemic (n=173) or presenting with high TG (≥1.7 mmol/liter) and low HDLc [<1.02 (men) or 1.28 mmol/liter (women)] (n=148) to investigate the impact of 13 polymorphisms of 9 genes affecting lipid metabolism (APOA5, APOC3, LPL, CETP, HL, MTP, APOE, LRP5, and VLDLR genes). The polymorphism rs328 in LPL was 40% significantly more frequent in normolipidemics (p=0.018), and in the same group, polymorphisms rs708272 in CETP and rs1800588 in HL were 10% significantly more frequent (p=0.037 for both polymorphisms). Patients who presented a combination of one to six alleles from these polymorphisms had 10% increased HDLc levels [1.13 (0.40) vs. 1.24 (0.23) mmol/liter, p=0.002] and a trend toward lower triglycerides [2.23 (2.34) vs. 1.89 (1.24) mmol/liter] and lower remnant-like particle cholesterol (RLPc) [16.41 (11.42) vs. 12.99 (11.69) mmol/liter]. This effect was dependent on the number of protective alleles and independent of the regimen administered. Polymorphisms in LPL, CETP, and HL protect HIV-infected patients from developing the dyslipidemia derived from high TG and low HDLc levels in a dose-dependent manner.
authors.affiliation: 1 Unitat de Recerca en Lípids i Arteriosclerosi, CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili , Reus, Spain .
authors.forename: Montse
authors.initials: M
authors.lastname: Guardiola
authors.affiliation: 2 Fundació Lluita contra la Sida, Hospital Universitari Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona , Barcelona, Spain .
authors.forename: Patricia
authors.initials: P
authors.lastname: Echeverria
authors.affiliation: 1 Unitat de Recerca en Lípids i Arteriosclerosi, CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili , Reus, Spain .
authors.forename: Marta
authors.initials: M
authors.lastname: González
authors.affiliation: 1 Unitat de Recerca en Lípids i Arteriosclerosi, CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili , Reus, Spain .
authors.forename: Joan C
authors.initials: JC
authors.lastname: Vallvé
authors.affiliation: 2 Fundació Lluita contra la Sida, Hospital Universitari Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona , Barcelona, Spain .
authors.forename: Jordi
authors.initials: J
authors.lastname: Puig
authors.affiliation: 2 Fundació Lluita contra la Sida, Hospital Universitari Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona , Barcelona, Spain .
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.affiliation: 1 Unitat de Recerca en Lípids i Arteriosclerosi, CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili , Reus, Spain .
authors.forename: Josep
authors.initials: J
authors.lastname: Ribalta
authors.affiliation: 2 Fundació Lluita contra la Sida, Hospital Universitari Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona , Barcelona, Spain .|3 Universitat de Vic-Universitat Central de Barcelona , Barcelona, Spain .
authors.forename: Eugènia
authors.initials: E
authors.lastname: Negredo
mesh_terms: D000483:Alleles; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D003430:Cross-Sectional Studies; D050171:Dyslipidemias / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000235:genetics*; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; C504173:LIPC protein, human; D008049:Lipase; C548261:LPL protein, human; D008071:Lipoprotein Lipase