PPARγ2 Pro12Ala polymorphism was associated with favorable cardiometabolic risk profile in HIV/HCV coinfected patients: a cross-sectional study

Journal of Translational Medicine

Salvador Resino¹  Dariela Micheloud³  Juan Carlos López⁴  Teresa Aldámiz-Echevarria²  Pilar Miralles⁴  Mónica García–Alvarez¹  María Ángeles Jiménez-Sousa¹  Daniel Pineda-Tenor¹  Amanda Fernández-Rodríguez¹  Juan Berenguer²  Pilar García-Broncano¹ 

[1] 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;Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid 28007, Spain;Servicio de Medicina Interna, Hospital General Universitario “Gregorio Marañón”, Madrid 28007, Spain;Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Marañón”, Madrid 28007, Spain

关键词: Single nucleotide polymorphism;    Fibrosis;    Insulin resistance;    Adipokines;    Serum lipids;    HIV/HCV coinfection;   

Others  :  1148353
DOI  :  10.1186/s12967-014-0235-9

 received in 2014-06-22, accepted in 2014-08-20,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 García-Broncano et al.; licensee BioMed Central Ltd.

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