Key result
Molecular analysis identifies novel genes including proline rich 11 as polygenic hypertension triggers in rats.
Novel genes not previously known to be involved in blood pressure modulation were identified as primary triggers for polygenic hypertension in rat models, revealing new pathways for BP homeostasis.
No direct clinical translation from rat models; leaves open new genetic targets for human polygenic hypertension.
OBJECTIVES: The discovery of causative genes leading to hypertension in animal models can reveal new mechanistic insights into blood pressure (BP) regulations. Previously, we isolated segments that harbor BP quantitative trait loci (QTLs) on rat chromosome 10 as defined by congenic strains made from crosses of inbred hypertensive Dahl salt-sensitive (DSS) and normotensive Lewis rats. The aim of the current study was to identify hypertension-causing genes for each QTL. METHODS: Molecular analysis was performed. RESULTS: A systematic and comprehensive molecular analysis divulged particular genes that carry nonconserved mutations. Specifically, the proline rich 11 gene is likely responsible for C10QTL5. C10QTL1 is one of five genes, namely Benzodiazepine receptor associated protein 1, Loc689764, myotubularin related protein 4, protein phosphatase 1E, PP2C domain containing and ring finger protein 43. Loc100363423 with no known function is a candidate for C10QTL3. The ATP-binding cassette, subfamily A (ABC1), member 8a gene is probably responsible for C10QTL2. CONCLUSIONS: Primary genes initiating polygenic hypertension are those not known to be involved in BP modulation. Novel pathways towards BP homeostasis appear to underlie the functionality of C10QTL5, C10QTL1 and C10QTL3 and C10QTL2. Moreover, these genes may become innovative targets for the diagnosis and therapeutics of essential hypertension.
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Chauvet et al. (2011) studied Hypertension. Molecular analysis of blood pressure quantitative trait loci (QTLs) was evaluated on Identification of hypertension-causing genes for each QTL. Molecular analysis identified novel genes, including proline rich 11 and Benzodiazepine receptor associated protein 1, as primary triggers for polygenic hypertension in rat models.
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