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Back To Vidyya Scientists Discover Gene Alteration That Hastens Onset Of AIDS

Findings Published In The Proceedings Of The National Academy Of Sciences

Scientists report this week that people who inherit a single, relatively common alteration in a human gene tend to progress more rapidly to AIDS than those born without the alteration. This week's finding, published in the Proceedings of the National Academy of Sciences, marks the tenth genetic alteration identified by scientists in the past four years that plays a role in slowing or hastening the onset of AIDS.

The gene, called IL10, short hand for interleukin-10, encodes a powerful cytokine, a protein that immune cells called lymphocytes excrete to regulate the intensity and duration of an immune response. IL10 is known as a potent inhibitor of HIV-1 and the growth of lymphocytes.

According to Stephen J. O'Brien, Ph.D., a senior author on the study and a scientist at the National Cancer Institute (NCI) at Frederick, the newly identified alteration lies within the so-called promoter region of the IL10 gene. A promoter is a gene's rheostat, helping to regulate the quantity of protein that it will produce in different tissues.

O'Brien said the alteration, or gene variant, appears to reduce the quantity of IL10 produced. He said this might result in increased HIV-1 replication and rapid progression to AIDS in people with the variant, called IL10-5'A.

In the study, O'Brien and colleagues analyzed IL10 genes from over 3,300 people whose HIV status has been tracked from 10 to 20 years. The scientists report that in the study the HIV-1/AIDS susceptibility IL10-5'A genotype was found in all races, including 41 percent of European Americans, 64 percent of African Americans, 84 percent of Asians, and 54 percent of Hispanics.

Michael W. Smith, Ph.D., also a senior author on the study and a scientist at the NCI at Frederick, said the discovery has important implications in establishing that IL10, an inhibitory cytokine, is a critical regulator in slowing the progression to AIDS, a process that takes on average 10 years after a person is infected with HIV-1. He said the results raise the prospect of IL10-based therapy as a new approach to treating people who are HIV positive.

The NCI's Laboratory of Genomic Diversity, which O'Brien heads, has described eight of the 10 genetic variants reported to date that influence the rate at which a person progresses to AIDS. The primary lead author of the study is Hyoung Doo Shin, Ph.D., who led the study as a member of the Laboratory of Genomic Diversity. Today, he serves as the chief executive officer of SNP Genetics, a genome-based biotechnology company in Seoul, Korea.

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Editor: Susan K. Boyer, RN
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