Association between AIDS disease progression rates and the Fok-I polymorphism of the VDR gene in a cohort of HIV-1 seropositive patients.
In addition to its role in mineral metabolism, 1,25-dihydroxivitamin D3 (1,25(OH)2D3) also has immunomodulatory effects. Vitamin D receptor (VDR) mediates genomic actions of 1,25(OH)2D3, by acting as a transcription factor that modulates the expression of several 1,25(OH)2D3 response genes. Variations at the VDR locus have been associated with susceptibility and progression to several immune diseases. We investigated the association between rates of progression to acquired immunodeficiency syndrome (AIDS) and the Fok-I polymorphism, which is located at the initiation codon of the VDR gene. The study was performed with a cohort of 185 patients infected with human immunodeficiency virus type 1 (HIV-1): all belonged to the intravenous drug abuse risk group. Progression to AIDS was according to the Centers for Disease Control 1993 criterion (CDC-1993). In addition, a first drop in CD4 cell count to below 200 microL(-1) was considered as outcome. Patients who reached outcomes during follow-up were considered progressors. Non-progressors were those patients remaining outcome-free after a minimum follow-up of 8 years. Heterozygous at the Fok-I polymorphism were over-represented in the group of patients that progressed to AIDS CDC-1993 (50% of progressors versus 36% of non-progressors, P=0.061; risk ratio (RR)=1.38 (95% confidence interval (CI): 0.98-1.96)) and in the group of patients that showed a drop in CD4 cell count to below 200 microL(-1) (52% of progressors versus 36% of non-progressors, P=0.037; RR=1.44 (95% CI: 1.02-2.03)). Mean time to AIDS CDC-1993 was shorter for those with Ff genotype than for those with FF and ff genotypes (non-Ff genotype patients), (log rank test P=0.035; Cox hazard ratio (HR) for Ff versus non-Ff=1.53 (95% CI: 1.0-2.33), P=0.047). In addition the drop in CD4 cell count to below 200 microL(-1) was reached faster in Ff carriers than in non-Ff patients (log rank test P=0.015; HR for Ff versus non-Ff=1.77 (95% CI: 1.12-2.8), P=0.014). According to these results, HIV-1 seropositive patients carrying the Ff genotype could be considered prone to a faster progression to AIDS.
Nieto
Gema
G
Unitat de Genètica Humana del Departament de Ciències Mèdiques Bàsiques de la Facultat de Medicina de la Universitat de Lleida, C/Montserrat Roig 2, 25199 Lleida, Catalunya, Spain.
Barber
Yolanda
Y
Rubio
Maria Carmen
MC
Rubio
Manuel
M
Fibla
Joan
J
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000503:physiopathology; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*
D018167:Receptors, Calcitriol; C035042:endodeoxyribonuclease FokI; D015252:Deoxyribonucleases, Type II Site-Specific