RESUMEN
This study evaluated the impact of 9 single nucleotide polymorphisms (SNPs) in 6 candidate genes (APOB, APOA5, APOE, APOC3, SCAP, and LDLR) over dyslipidemia in HIV-infected patients on stable antiretroviral therapy (ART) with undetectable viral loads. Blood samples were collected from 614 patients at reference services in the cities of Porto Alegre, Pelotas, and Rio Grande in Brazil. The SNPs were genotyped by conventional polymerase chain reaction (PCR) and real-time PCR. The prevalence of dyslipidemia was particularly high among the protease inhibitors-treated patients (79%). APOE (rs429358 and rs7412) genotypes and APOA5 -1131T>C (rs662799) were associated with plasma triglycerides (TG) and low-density-lipoprotein cholesterol levels (LDL-C). The APOA5 -1131T>C (rs662799) and SCAP 2386A>G (rs12487736) polymorphisms were significantly associated with high-density-lipoprotein cholesterol levels. The mean values of the total cholesterol and LDL-C levels were associated with both the APOB SP Ins/Del (rs17240441) and APOB XbaI (rs693) polymorphisms. In conclusion, our data support the importance of genetic factors in the determination of lipid levels in HIV-infected individuals. Due to the relatively high number of carriers of these risk variants, studies to verify treatment implications of genotyping before HAART initiation may be advisable to guide the selection of an appropriate antiretroviral therapy regimen.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa/estadística & datos numéricos , Dislipidemias/epidemiología , Dislipidemias/genética , Marcadores Genéticos/genética , Infecciones por VIH/genética , Infecciones por VIH/prevención & control , Adulto , Brasil/epidemiología , Comorbilidad , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Infecciones por VIH/epidemiología , Humanos , Masculino , Polimorfismo de Nucleótido Simple/genética , Prevalencia , Factores de Riesgo , Carga Viral/estadística & datos numéricosRESUMEN
OBJECTIVE: To investigate genetic single nucleotide polymorphisms (SNPs) in estrogen receptor-α (ERα) (ESR1, rs2234693, rs1801132, rs7757956 and rs2813544) and ERß (ESR2, rs3020450, rs7154455 and rs4986938) genes and relate them to the adverse effects lipodystrophy, dyslipidemia and metabolic syndrome as well as to differences in their prevalence between sexes in HIV-infected individuals on HAART. DESIGN: Cross-sectional study. METHODS: Blood samples and anthropometric measurements were collected from 614 patients at reference services in the cities of Porto Alegre, Pelotas and Rio Grande in Brazil. The SNPs were genotyped by real-time PCR. RESULTS: The lipodystrophy subtype frequencies in patients of different sexes showed statistically significant differences; the atrophic pattern was more prevalent in men, and the hypertrophic pattern was more prevalent in women. Furthermore, metabolic syndrome prevalence was higher in women than in men. The ESR1 rs2813544 G-allele was associated with higher measurements of several anthropometric variables in women: BMI, total subcutaneous fat and subcutaneous fat of limbs. Additionally, patients who were AA homozygous for ESR2 rs3020450 presented an increased risk for developing lipoatrophy (prevalence ratio 1.37, 95% confidence interval 1.09-1.73, P = 0.007). CONCLUSION: Significant differences in lipodystrophy and metabolic syndrome prevalence were detected between sexes. Moreover, the ESR1 gene (rs2813544) presented significant sex-specific associations with anthropometric variables, and the ESR2 gene (rs3020450) was associated with an increased risk of developing lipoatrophy. Our results suggest that these genes are in part responsible for the sexual dimorphism in fat tissue redistribution and patterns of lipodystrophy.
Asunto(s)
Terapia Antirretroviral Altamente Activa/efectos adversos , Distribución de la Grasa Corporal , Dislipidemias/genética , Receptor alfa de Estrógeno/genética , Infecciones por VIH/genética , Síndrome de Lipodistrofia Asociada a VIH/genética , Síndrome Metabólico/genética , Polimorfismo de Nucleótido Simple , Adulto , Análisis de Varianza , Índice de Masa Corporal , Brasil/epidemiología , Estudios Transversales , Dislipidemias/virología , Receptor alfa de Estrógeno/metabolismo , Femenino , Genotipo , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Cumplimiento de la Medicación , Síndrome Metabólico/virología , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores SexualesRESUMEN
Highly active antiretroviral therapy (HAART) has increased the survival of HIV-infected patients. However, adverse effects play a major role in adherence to HAART. Some protease inhibitors (mainly atazanavir and indinavir) act as inhibitors of uridine diphosphate-glucuronosyltransferase (UGT1A1), the enzyme responsible for hepatic conjugation of bilirubin. Variations in the promoter region of the UGT1A1 gene (UGT1A1*28, rs8175347) can influence bilirubin plasma levels, modulating the susceptibility to hyperbilirubinemia. Aiming to analyze the association between UGT1A1*28 allele and hyperbilirubinemia in individuals exposed to HAART, we evaluated 375 HIV-positive individuals on antiretroviral therapy. Individuals carrying the UGT1A1*28 allele had a higher risk of developing severe hyperbilirubinemia [prevalence ratio (PR)=2.43, 95% confidence interval (CI) 1.08-5.45, p=0.032] as well as atazanavir users (PR=7.72, 95% CI=3.14-18.98, p<0.001). This is the first description of such an association in Brazilian HIV patients, which shows that in African-American and Euroamerican HAART users, the UGT1A1*28 allele also predisposes to severe hyperbilirubinemia, especially in those exposed to atazanavir.