Analysis of CCR5, CCR2, SDF1 and RANTES gene polymorphisms in subjects with HIV-related PML and not determined leukoencephalopathy.
Progressive Multifocal Leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system (CNS) caused by JC virus (JCV), a human polyomavirus that can lytically infect and destroy the oligodendrocites in immunosuppressed individuals. After the introduction of highly active antiretroviral therapy (HAART) for AIDS treatment, a PML-like leukoencephalopathy, known as non-determined leukoencephalopathy (NDLE), has also been observed. Since a number of host genetic factors have been identified as having an impact on susceptibility to HIV-1 infection and in the progression to AIDS and death, in this work we analysed the pattern of distribution of different chemokine and chemokine receptor polymorphisms that seem to be involved in HIV+ neurological diseases. The CCR5, RANTES, CCR2 and SDF1 genes were molecularly analysed in 84 HIV+ HAART treated subjects: 55 without neurological disorders (HIV+), 12 HIV+ NDLE and 17 HIV+ PML patients. The RANTES -403 G/A polymorphism was significantly associated with NDLE. These data suggest that mutation of the RANTES allele can predispose to the induction of demyelination similarly to what has been observed in Multiple Sclerosis (MS) and may suggest a possible explanation for the development of leukoencephalopathy without detection of JCV.
Guerini
Franca R
FR
Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, S. Maria Nascente, Milan, Italy. fguerini@dongnocchi.it
Delbue
Serena
S
Zanzottera
Milena
M
Agliardi
Cristina
C
Saresella
Marina
M
Mancuso
Roberta
R
Maserati
Renato
R
Marchioni
Enrico
E
Gori
Andrea
A
Ferrante
Pasquale
P
D000328:Adult; D000368:Aged; D000483:Alleles; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D002493:Central Nervous System Diseases / Q000209:etiology / Q000235:genetics; D018946:Chemokine CCL5 / Q000235:genetics; D054377:Chemokine CXCL12 / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000150:complications / Q000235:genetics*; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D054390:Receptors, CCR2 / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics
D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D054390:Receptors, CCR2; D019713:Receptors, CCR5