The Distribution Of Stromal Derived Factor–1 Mutation In Kenyan Population

ABSTRACT

Human immunodeficiency virus type-1 (HIV-1) appeared on the scene over twenty years ago and has since caused many deaths; left millions orphaned and created uncertainty in any families. The virus has also created a socio-economic burden to many countries. The entry into and tropism of the host immune cells by the HIV-1 depends on chemokine receptors and coreceptor interactions among other factors. Genetic polymorphism in chemokine receptors and coreceptor genes influences susceptibility to HIV-1 infection and disease progression. Polymorphisms in the stromal derived factor-1 (SDF-1) play an important role in the evolution of HIV-1 in patients. The mutant SDF-1 (stromal derived factor-1 3A`/3A`) competes with the virus for the coreceptor site CXCR4 on the CD4+ Tcells therefore down-regulating evolution of non-syncytial to syncytial induction during HIV-1 progression. The occurrence of SDF-1 3‟A in populations varies between races, with blacks having 11% and whites having 37% in the USA. In India, SDF-1 mutations are rated between 25% and 38% while in East Asia they are rated between 3% and 67%. Caucasians have the highest frequency of the SDF-1 3‟A/3‟A mutations. South African Sotho and Xhosa tribes had 1% and 2.8% of this mutation respectively. In this study, a survey on the distribution of SDF-1 gene polymorphisms in the Kenyan provinces was conducted with a view of trying to check any genetic basis for variations in HIV and AIDS regional prevalence rates. Two hundred whole blood samples were collected from eight provinces of Kenya and analysed at the Kenya Medical Research Institute in Nairobi. Detection of SDF-1 gene polymorphisms was done by extraction of proviral DNA from whole blood and the SDF-1 target gene was amplified by polymerase chain reaction (PCR) using gene-specific primers. The different SDF-1 gene polymorphisms were detected by Restriction Fragment Length Polymorphism (RFLP) and gel electrophoresis. Two DNA bands were visualized at 202 and 100 base pairs for the homozygous dominant polymorphism (wild type), three bands of 302, 202 and 100 base pairs (heterozygous) and one band at 302 base pair for the mutant alleles. Chi-square test was used to compare the distributions of these mutations in the eight provinces as Pearson‟s moment of correlation coefficient was used to correlate the SDF-1 mutation with HIV incidences in the eight provinces of Kenya. The data generated was used to calculate percentage distribution of the mutation per province. This study showed the presence of the stromal derived factor-1 polymorphism in Kenyan population with an average of 6.6% for the double mutant, 20.7% for heterozygous and 73.7% for the wild type. There was no correlation between the HIV prevalence and the SDF-1 distribution in Kenya; interestingly, Nyanza province recorded a high occurrence of the SDF-1 3‟A/3‟A (11.11%) double mutants but is also had the highest HIV prevalence (15.3%). The results obtained in this study will form a foundation for further research given that double mutants have been found to show some resistance to HIV infection. Since mutants show good response to anti-retroviral drugs, researchers can also incorporate genetics into the treatment of HIV.