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Genetic mutation increases risk of dementia in HIV patients
The human immunodeficiency virus (HIV) wreaks havoc in the brain, in addition to its other devastating effects. With the advent of the AIDS epidemic, especially in Africa, HIV-associated dementia has become one of the most common causes of dementia in the world, along with vascular dementia and Alzheimer's dementia. HIV-1 infection accounts for a sharp rise in dementias in persons 40 and under.
Novel research, featured in the Proceedings of the National Academy of Sciences-USA early online edition for the week of Sept. 30, points to a gene mutation that more than quadruples the risk of HIV-associated dementia. Sunil K. Ahuja, M.D., of The University of Texas Health Science Center at San Antonio (UTHSCSA) and co-authors including Lt. Col. Matthew Dolan of Wilford Hall Medical Center, San Antonio, describe a key role for a protein called MCP-1 (monocyte chemoattractant protein-1). The finding, obtained by studying blood samples from 1,115 adults and 592 children with HIV, is one explanation as to why some AIDS patients quickly progress to dementia, others develop it more slowly and some never do.
"It's a double-edged sword," said Dr. Ahuja, professor of medicine, microbiology and immunology at UTHSCSA. "We showed that people with two copies for a mutation in the MCP-1 gene have a 50 percent lower risk of being infected with HIV-1. But, paradoxically, our findings also suggest that once HIV infection has been established, the same genetic profile is associated with accelerated disease progression and increased risk of HIV-associated dementia." The risk appears to be linked to increased production of the MCP-1 protein by the mutated genes, he said.
The MCP-1 protein activates infection-fighting cells in the brain and elsewhere, resulting in inflammation and tissue injury, and it also seems to encourage HIV to replicate, the scientists reported. "Our findings offer the potential for assessing which patients have a higher risk of developing HIV-associated dementia," Dr. Ahuja said. "More study is needed to determine if we can use this mutation as a screening tool to consider the early initiation of AIDS drugs that achieve high concentrations in the brain."
The paper also provides clues that the MCP-1 protein is crucial in other neurodegenerative disorders, such as Alzheimer's disease and multiple sclerosis. "In a broader context, our findings provide the impetus to understand the influence of genetic variation in MCP-1 in susceptibility to Alzheimer's disease, multiple sclerosis and even in other disorders, such as coronary artery disease and asthma," Dr. Ahuja said.
The National Institutes of Health and the U.S. Department of Veterans Affairs provided research funding. Dr. Ahuja is the director of the VA AIDS/HIV Research Center at the Audie Murphy Division of the South Texas Veterans Health Care System.
Note: Co-authors are from The University of Texas Health Science Center at San Antonio; the South Texas Veterans Health Care System, San Antonio; Ohio State University; the Laboratorio de Biologia Celular y Retrovirus and Servicio de Infectologia, Hospital de Pediatria, Buenos Aires, Argentina; Forest Laboratories, New York; the University of Utah; and Wilford Hall Medical Center in San Antonio. They are Enrique Gonzalez, Brad Rovin, Luisa Sen, Glen Cooke, Rahul Dhanda, Srinivas Mummidi, Hemant Kulkarni, Michael Bamshad, Vanessa Telles, Stephanie Anderson, Elizabeth Walter, Kevin Stephan, Michael Deucher, Andrea Mangano, Rosa Bologna, Seema Ahuja, Matthew Dolan and Sunil Ahuja.
A copy of the journal article is available by calling the Proceedings office at (202) 334-1310.
Contact: Will Sansom