Genetic polymorphisms of interleukin-receptor antagonist (IL-1RA) gene among HIV infected and non-infected individuals in Nairobi
Mutheca, Irene Wanjiru
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Interleukin-l (IL-l) and its endogenous antagonist IL-l receptor antagonist (IL-l RA) play an important role in various inflammatory responses. They are both produced in chromosome two and their production is different between men and women. The Human Immunodeficiency Virus (HIV) utilizes IL-l and viral tat protein to accelerate its replication and the synthesis of all HIV proteins. Interleukin-l receptor antagonist gene has been shown to retard HIV disease progression by inhibiting HIV replication mediated by IL-l. Understanding the mechanisms that account for the lower viral loads in some individuals is important for designing of new antiviral drugs or vaccines which may be achieved by blocking the effects of IL-l. In intron 2 of the IL-l RA gene, a variable number of an 86-bp tandem repeat polymorphism leads to the existence of five different alleles. Distribution of the IL-l RA gene polymorphism within a population can be considered as a. measure of genetic susceptibility of HIV infection and disease progression. This study sought to determine the frequency of IL-l RA gene polymorphisms in a population of HIV infected and non-infected men and women in Nairobi. Two hundred and forty samples were collected of which 170 samples were HIV positive and 70 samples were from HIV negative individuals. Peripheral blood mononuclear cells were extracted from whole blood. Genomic deoxyribonucleic acid was then extracted from PBMCs. The genotypes and alleles of IL-l RA were determined by polymerase chain reaction (PCR) using specific primers. All the PCR amplicons were analysed using 2% gel electrophoresis. Allele and genotype frequencies were calculated by direct counting. Chi square test was used in comparing frequency of alleles between infected and non-infected individuals. Four alleles were identified in the study group with allele 1 having the highest occurrence of 80.59%, allele 2 (4.71%), allele 3 (5.88%) and allele 4 (8.82%). In the control group, only two alleles were observed with allele 1 (74.3%) and allele 4 (25.7%). Several genotypes were observed and they were different between the study and control groups and also in men and women. The results showed that there was a gender difference in IL-l RA gene polymorphism expressed by a higher incidence of genotype 1/1 homozygotes in men (71.8%) and a higher occurrence of genotype 2/2 homozygotes in women (5.9%). Allele 1 and 4 were more frequent in men, while allele 2 and 3 were more prevalent in women. These data might hold the key to developing appropriate strategies for effective response of those who appear to be immune to HIV. Since the functional significance of this polymorphisms remains unclear, further investigations into a possible correlation between specific IL-l RA genotypes and alleles and HIV is necessary, with a view to a possible new therapeutical approach in treatment of HIV especially the use of protective IL-l RA alleles.
- MST-Zoological Sciences