Variations in a gene, MBL2, either protected against the disease or caused susceptibility
A majority of Indians are susceptible to malaria while certain tribal groups in the country have resistance to the disease, thanks to mutations in a single gene that determine an individual’s proneness or resistivity.
A new study carried out by scientists from the CSIR-Centre for Cellular and Molecular Biology (CCMB) and the Institute of Tropical Medicine, Germany, found that variations in the gene, MBL2, were responsible either for protecting against the disease or making an individual susceptible.
The study done by Aditya Nath Jha et al, was published in the January 2014 issue of Infection and Immunity, an American journal.
Pointing out that malaria was one of the major causes for morbidity and mortality in tropical and sub-tropical countries, it was noted in the study that an estimated 1.24 million deaths were caused by the disease in 2010, mostly in Africa.
Mentioning about the pathogenesis of malaria, it observed that the severity depends on the complex interplay between host genetic make-up, the parasite’s virulence, its transmission dynamics as well as host immune responses.
Apart from malaria, MBL2 genetic variations were earlier associated with various infectious diseases like leishmaniasis, leprosy, schistosomiasis, trypanosomiasis, HIV and auto-immune diseases.
Dr. Thangaraj, senior scientist at CCMB said MBL2 was a pathogen recognizing molecule and usually binds to the surface of glycoconjugate, one of the proteins on the surface of pathogens.
In the case of malaria, it adheres to the malarial parasite and activates the body’s defence mechanism.
“This gene is a pathogen receptor molecule and has a lot of functions in immunity. For the first time, we have looked at its role in malaria in Indian population,” he said.
The scientists conducted a DNA analysis of the entire MBL2 gene in 434 malaria patients from regions that were endemic to the disease. Additionally, 830 individuals from 32 socially, linguistically and geographically diverse endogamous Indian populations were investigated for distribution of MBL2 variations. The study found that around 20 per cent of severe malaria patients carried structural variants of the gene. The frequency of variations was three times more when compared to the control subjects.
Interestingly, the scientists found a combination of variants that give protection against malaria in some tribal groups such as Gonds and Subba. Both the groups had high level of MBL2 and also the structural variants that offer protection.
Other groups such as Lambadis, Rajgonds, Puma and Sherpas had higher frequency of MBL2*Y mutation which made them susceptible to the disease.
Dr. Thangaraj said this was the first evidence to show that some population had naturally selected gene variants to protect against malaria. It could be true of other infectious diseases too.
Apparently that population at some time was exposed to malaria and they subsequently developed genes resistant to the disease through the process of natural selection.
With the CCMB Director, Ch. Mohan Rao emphasising on the need for taking up socially-relevant research, this study is a step in that direction and could help in future in developing drugs.