The relevance of population specific standardisation in the analysis of specific type 2 diabetes mellitus genetic susceptibility loci

Thesis (Ph.D. (Biochemistry))--North-West University, Potchefstroom Campus, 2005.Type 2 diabetes mellitus (T2D) is currently one of the fastest growing non-communicable diseases in the world. It is induced by the pathogenic interaction between insulin resistance and secretion. There are numerous forms of these disorders which are characterised by hyperglycaemia and affect approximately 4% of the general population. This percentage is however rapidly increasing especially in developing regions such as sub-Saharan Africa and Latin America. During this investigation two diabetic cohorts and two control cohorts consisting of adult black Southern African and Cuban individuals respectively, were screened for reported single nucleotide polymorphisms (SNPs) within the adiponectin and calpain 10 genes. Genotyping was achieved via a real time PCR strategy. Frequency differences between the various genetic configurations of the two cohorts were calculated utilising appropriate statistical analyses. With regards to the black Southern African cohort, it was determined that certain factors in the calpain 10 gene, e.g. the wild type homozygote at UCSNP-56, were associated with protection towards T2D. Investigation of the Cuban cohort alternatively resulted in the elucidation that this group presents with a differential risk pattern than that of the reported European populations. Analysis of the adiponectin gene resulted in the determination that within the South African cohort, the G-11391A locus and the 11/12 haplotype combination were associated with protection towards T2D. The variant allele homozygote at the C-11377G locus was associated with increased disease risk within the Cuban cohort investigated. The associations detected in the aforementioned genes were not maintained upon meta-analysis. When compared to various non-African populations, the investigated SNPs have population specific effects in T2D susceptibility depending on the population investigated. This is most likely due to certain epistatic factors, determination of which will be integral to future investigations of T2D. Data from this investigation indicates that the elucidation and implementation of prevention strategies should be population specific.Doctora