HIV patients in Africa with a specific genetic variant have much lower rate of tuberculosis ;
The first known discovery of this type, a School Team Medicine led by Case Western Reserve University has found that HIV patients in Africa with a genetic variant have a chance some 63 percent lower risk of developing tuberculosis than HIV patients without the gene variant.
“This discovery could pave the way for the development of new treatments against tuberculosis, which can be effective in both HIV-positive and the general population individuals,” said lead author of the study, Scott M. Williams, PhD, visiting professor in the department of epidemiology and biostatistics at the School of Medicine at Case Western Reserve University.
The study, published in the March issue of The American Journal of Human Genetics , a team of researchers from the United States, Africa, Japan and Europe studied the genetic profiles of 581 Ugandans living with HIV and Tanzanians , 267 of whom developed active tuberculosis, and 314 who did not. They found that the latter group was significantly more likely to carry a genetic variant of the IL12B gene near coding for a protein called interleukin-12, which is present in all people and helps kill pathogens by stimulating the immune response that fights infection. In fact, those who carried the variant had a 63 percent reduction in the risk of TB when exposed to the bacteria that causes tuberculosis. “The genetic variation we found seems to affect this important protein, whether produced more interleukin 12 or a different version of the same, or perhaps a combination of the two,” Williams said. “We believe this may be the reason for the much higher level of resistance to tuberculosis we found. We will carry out more work to determine which of these three possible explanations is correct.”
Previous studies have shown a deficient gene IL12B predisposes patients to TB. This is the first study known to find that patients with a genetic variant of the gene are associated with protection against TB. All previous studies of human genetic susceptibility to tuberculosis have excluded patients with HIV or adjusted by him as a potential confounder in the analysis; School of Medicine-led is the first to focus exclusively on HIV patients in relation to tuberculosis.
This study is also unique in demonstrating that a relatively small sample can produce a statistically significant result of such magnitude. “Usually studies on the genetic relationship of tuberculosis involving 10,000 or more,” Williams said. “In these cases, genetic effects have been associated with five percent, in exchange for twenty percent risk of TB. Our findings of an increase of 63 percent protection against TB are a significant departure from these other studies.”
The study population consisted of patients with HIV in Tanzania that were likely to have been exposed to tuberculosis because they were living in a crowded urban area in a country with a high incidence of tuberculosis and HIV patients Uganda to be with family members diagnosed with TB (ie, the study group was exposed to tuberculosis on a regular basis).
Tuberculosis is caused by a bacterium called Mycobacterium tuberculosis (MTB). The bacteria usually attack the lungs, but other parts of the body such as the kidneys, spine and brain are susceptible too. If not treated properly, TB can be fatal. The disease is spread through the air when a person with TB of the lungs or throat coughs, sneezes, speaks, spits, or sings. People nearby may breathe in these bacteria and become infected. TB is not spread by shaking hands, sharing food or drink, or kiss.
According to the World Health Organization in 2014, 9.6 million people became ill with tuberculosis and 1.5 million died of the disease. About a third of the world’s population is latently infected with MTB, which means they have been infected with MTB bacteria but are not (yet) ill with the disease and can not transmit. These people have a lifetime risk of ten percent of developing TB. However, people with compromised immune systems, such as those living with HIV, malnutrition or diabetes, or people who use snuff, have a much higher risk of disease. People who are infected with HIV are 20 to 30 times more likely to develop active TB and one in three HIV deaths worldwide is estimated to be due to tuberculosis. The disease occurs in all parts of the world, but is most common in Africa, with 281 cases per 100,000 people in 2014 (compared to a world average of 133).
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