title: PPARγ2 Pro12Ala polymorphism was associated with favorable cardiometabolic risk profile in HIV/HCV coinfected patients: a cross-sectional study.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor gamma-2 gene (PPARγ2) rs1801282 (Pro12Ala) polymorphism has been associated with lower risk of metabolic disturbance and atherosclerosis. The aim of this study was to analyze the association between the Pro12Ala polymorphism and cardiometabolic risk factors in human immunodeficiency virus (HIV)/Hepatitis C virus (HCV)-coinfected patients.
  
  
  METHODS
  We carried out a cross-sectional study on 257 HIV/HCV coinfected patients. PPARγ2 polymorphism was genotyped by GoldenGate® assay. The main outcome measures were: i) serum lipids (cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), LDL-C/HDL-C, and atherogenic index (AI)); ii) homeostatic model assessment (HOMA-IR) values; iii) serum adipokines (leptin, adiponectin, resistin, plasminogen activator inhibitor-1(PAI-1), hepatic growth factor (HGF), and nerve growth factor (NGF)). Generalized Linear Models (GLM) with gamma distribution (log-link) were used to investigate the association between PPARγ2 polymorphism and continuous outcome variables. This test gives the differences between groups and the arithmetic mean ratio (AMR) in continuous outcome variables between groups.
  
  
  RESULTS
  The rs1801282 CG/GG genotype was associated with low values of cholesterol (adjusted arithmetic mean ratio (aAMR) = 0.87 (95% of confidence interval (95% CI) = 0.79; 0.96); p = 0.004) and LDL-C (aAMR = 0.79 (95% CI = 0.68; 0.93); p = 0.004). Furthermore, rs1801282 CG/GG was associated with low values of HOMA-IR (aAMR = 0.69 (95% CI = 0.49; 0.98); p = 0.038) among patients with significant liver fibrosis (F ≥ 2). Moreover, rs1801282 CG/GG was also associated with low serum values of hepatic growth factor (HGF) (aAMR = 0.61 (95% CI = 0.39; 0.94); p = 0.028), and nerve growth factor (NGF) (aAMR = 0.47 (95% CI = 0.26; 0.84); p = 0.010). The serum levels of leptin, adiponectin, resistin, and PAI-1 did not show significant differences.
  
  
  CONCLUSIONS
  The presence of PPARγ2 rs1801282 G allele (Ala variant) was associated with a protective cardiometabolic risk profile versus CC genotype in HIV/HCV-coinfected patients. Thus, PPARγ2 rs1801282 polymorphism may play a significant role in the development of metabolic disorders in HIV/HCV coinfected patients, and might have an influence on the cardiovascular risk.
authors.forename: Pilar
authors.initials: P
authors.lastname: García-Broncano
authors.forename: Juan
authors.initials: J
authors.lastname: Berenguer
authors.forename: Amanda
authors.initials: A
authors.lastname: Fernández-Rodríguez
authors.forename: Daniel
authors.initials: D
authors.lastname: Pineda-Tenor
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Jiménez-Sousa
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Alvarez
authors.forename: Pilar
authors.initials: P
authors.lastname: Miralles
authors.forename: Teresa
authors.initials: T
authors.lastname: Aldámiz-Echevarria
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: López
authors.forename: Dariela
authors.initials: D
authors.lastname: Micheloud
authors.affiliation: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda- Pozuelo, Km 2,2, Majadahonda, Madrid 28220, Spain. sresino@isciii.es.
authors.forename: Salvador
authors.initials: S
authors.lastname: Resino
mesh_terms: D000328:Adult; D000409:Alanine / Q000235:genetics; D019943:Amino Acid Substitution; D002318:Cardiovascular Diseases / Q000150:complications / Q000235:genetics*; D060085:Coinfection; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D015497:HIV-1; D006526:Hepatitis C / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000150:complications / Q000235:genetics*; D055442:Metabolome / Q000235:genetics; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011392:Proline / Q000235:genetics; D012307:Risk Factors
chemical_list: D047495:PPAR gamma; D011392:Proline; D000409:Alanine