Increased Support for Linkage of a Novel Locus on Chromosome 5q13 for Essential Hypertension in the British Genetics of Hypertension Study

Abstract

Abstract-Human hypertension arises from a combination of genetic factors and lifestyle influences. With cardiovascular disease set to become the number 1 cause of death worldwide, it is important to understand the etiologic mechanisms for hypertension, because these might provide new routes to improved treatment. The British Genetics of Hypertension Study has recently published a primary genome screen that identified 4 chromosomal regions of interest. We have now genotyped additional markers to confirm the most promising regions for follow-up studies. Thirty-four additional microsatellites were genotyped in our severely hypertensive affected sibling pair resource (now 1635 families with 2142 affected sibling pairs), leading to a substantial increase in information content in the regions of interest. We found increased support for linkage of chromosome 5q13 to human hypertension (multipoint logarithm of oddsϭ2.50) with 3 adjacent markers yielding single point logarithm of odds scores of 3.22, 2.84, and 2.51. The placement of additional markers on 2q, 6q, and 9q diminished support for linkage in these regions. However, the addition of new data and families identified novel regions of interest on chromosomes 1q and 11q. The 3 positive markers in the chromosome 5 region were also genotyped in 712 distinct parent-offspring trios with the same severe phenotype to replicate linkage and association. Borderline support for replication was found (Pϭ0.07). We found increased evidence for linkage and borderline-significant evidence for association for a hypertension susceptibility locus on chromosome 5q13 that is worthy of detailed fine mapping and assessment of candidate genes. (Hypertension. 2006;48:105-111.)

Fibroblast Growth Factor 1 Gene and Hypertension

“…This type of fine mapping is fundamental in validation of positive linkage findings and narrowing down the QTL but is critically dependent on accuracy of microsatellite chromosomal locations. 26 Therefore, to exclude spurious linkage that may be driven by arbitrary definition of distances between microsatellite markers, we confirmed the multipoint findings in the complementary single-point analysis. Most importantly, the studies based on single microsatellite markers contributed to narrowing down the QTL to an extent that was dissectible in positional analysis.…”

Recommendations for the management of patients with obstructive sleep apnoea and hypertension

“…From family and epidemiological studies it is clear that a complex interplay between heritable and environmental factors such as dietary sodium intake, alcohol consumption, stress and body weight results in final expression of hypertension [53,54]. Limited data on the genetic contribution to the association between OSA and hypertension is available.…”

Position paper on the management of patients with obstructive sleep apnea and hypertension

“…From family and epidemiological studies, it is clear that a complex interplay between heritable and environmental factors such as dietary sodium intake, alcohol consumption, stress and body weight results in final expression of hypertension [53,54]. Limited data on the genetic contribution to the association between OSA and hypertension are available.…”