Role of the thiazide-sensitive sodium chloride cotransporter gene in primary hypertension associated with hypercalciuria.
Published: 2006
Language: eng
Number of pages: 142
ISBN-13: 9780494219751
Description: Hypertension is a common disease with major public health implications and complex genetic background. Abnormalities in renal sodium handling is a central feature of the pathogenesis of essential hypertension. The renal thiazide-sensitive sodium chloride cotransporter (TSC) is a major sodium and chloride transporter in the distal nephron. It is known to indirectly influence renal calcium handling and is involved in monogenic diseases that feature arterial hypotension or hypertension We hypothesize that genetic variations in the TSC gene are important in the pathogenesis of salt-sensitive essential hypertension associated with hypercalciuria through increased sodium transport.The objectives of this thesis are to: (1) test for linkage of hypertension and hypercalciuria to the chromosomal region harbouring the TSC gene, (2) search for genetic variants in the coding region of the gene and to study their effect on TSC function, and (3) test for an association of hypertension and hypercalciuria with intragenic marker alleles in the gene.Family based analysis did not show association to hypertension or hypercalciuria, emphasizing the need for further studies to resolve the controversy of the TSC's role in hypertension.Linkage analysis of families with hypercalciuric probands and a family history of hypertension, using five microsatellite markers spanning a 10 cM region on chromosome 16q13, demonstrated suggestive linkage to the TSC gene locus. We have found four non-synonymous single nucleotide polymorphisms by screening the coding region of the TSC gene in these families, and demonstrated that one of the variants causes increased sodium transport when expressed in a heterologous oocyte expression system. This variant may contribute to elevated blood pressure in individuals with this genetic abnormality.
Notes: Source: Dissertation Abstracts International, Volume: 68-01, Section: B, page: 0063.

Thesis (Ph.D.)--University of Toronto, 2006.

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