engleski

Genetic basis of hypertension studied in isolated population - example of the island Vis population

In this doctoral dissertation several analyses were conducted in order to identify genes for hypertension on chromosome 7 in isolated population of the island of Vis. The dissertation could be divided in three parts: in the first one, linkage analysis for hypertension as well as systolic and diastolic blood pressure with the markers on chromosome 7 was performed ; in the second, the association study of the polymorphisms within two candidate genes for hypertension (endothelial nitric oxide synthase gene, eNOS and leptin gene, LEP) and hypertension was performed ; in the third, in orer to assess the usefulness of Vis population for future association studies, the LD pattern and distribution along the chromosome 7 was compared between Vis population and HapMap (http://www.hapmap.org) population with European ancestry. The most important result is statistically very significant (p<0.0001) evidence of linkage of marker D7S2464 in region of 13 cM chromosome 7 with hipertension. Such statistically high evidence of susceptibility variant in this region is probably found due to genetic homogeneity of families collected in the population of Vis. Furthermore, the evidence of linkage was found in the region of 56 cM for both blood pressures - systolic and diastolic. The highest peak in the same region for both systolic and diastolic blood pressure suggests that this region should be considered further. We also found clear association of LEP G-2548A polymorphism with hypertension. Moreover, potential epistatic effect of leptin and eNOS gene was observed. The ancestral allele of LEP G-2548A was associated with hypertension which diminishes the possibility that it is the functional variant but its effect could be due to an unobserved variant in high LD with it. Finally, we did not fond the population of the island of Vis should be more suitable for future genome-wide association than classical, outbred populations. However, Vis population can still offer special benefit such as large pedigrees, the reduction in genetic, cultural and environmental heterogeneity and potential accumulation of specific susceptibility alleles, all of which show promise for linkage analyses in this population.

genes; hypertension; isolated population; island of Vis

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