Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma in Caucasians from the USA
HUMAN MOLECULAR GENETICS
Authors: Wiggs, Janey L.; Kang, Jae Hee; Yaspan, Brian L.; Mirel, Daniel B.; Laurie, Cathy; Crenshaw, Andrew; Brodeur, Wendy; Gogarten, Stephanie; Olson, Lana M.; Abdrabou, Wael; DelBono, Elizabeth; Loomis, Stephanie; Haines, Jonathan L.; Pasquale, Louis R.
Abstract
Primary open-angle glaucoma (POAG) is a genetically complex common disease characterized by progressive optic nerve degeneration that results in irreversible blindness. Recently, a genome-wide association study (GWAS) for POAG in an Icelandic population identified significant associations with single nucleotide polymorphisms (SNPs) between the CAV1 and CAV2 genes on chromosome 7q31. In this study, we confirm that the identified SNPs are associated with POAG in our Caucasian US population and that specific haplotypes located in the CAV1/CAV2 intergenic region are associated with the disease. We also present data suggesting that associations with several CAV1/CAV2 SNPs are significant mostly in women.
P/Q-type and T-type voltage-gated calcium channels are involved in the contraction of mammary and brain blood vessels from hypertensive patients
ACTA PHYSIOLOGICA
Authors: Thuesen, A. D.; Lyngso, K. S.; Rasmussen, L.; Stubbe, J.; Skott, O.; Poulsen, F. R.; Pedersen, C. B.; Rasmussen, L. M.; Hansen, P. B. L.
Abstract
Aim: Calcium channel blockers are widely used in cardiovascular diseases. Besides L-type channels, T-and P/Q-type calcium channels are involved in the contraction of human renal blood vessels. It was hypothesized that T-and P/Q-type channels are involved in the contraction of human brain and mammary blood vessels. Methods: Internal mammary arteries from bypass surgery patients and cerebral arterioles from patients with brain tumours with and without hypertension were tested in a myograph and perfusion set-up. PCR and immunohistochemistry were performed on isolated blood vessels. Results: The P/Q-type antagonist x-agatoxin IVA (10(-8) mol L-1) and the T-type calcium blocker mibefradil (10(-7) mol L-1) inhibited KCl depolarization- induced contraction in mammary arteries from hypertensive patients with no effect on blood vessels from normotensive patients. omega-Agatoxin IVA decreased contraction in cerebral arterioles from hypertensive patients. L-type blocker nifedipine abolished the contraction in mammary arteries. PCR analysis showed expression of P/Q-type (Ca(v)2.1), Ttype (Ca(v)3.1 and Ca(v)3.2) and L-type (Ca(v)1.2) calcium channels in mammary and cerebral arteries. Immunohistochemical labelling of mammary and cerebral arteries revealed the presence of Cav2.1 in endothelial and smooth muscle cells. Cav3.1 was also detected in mammary arteries. Conclusion: P/Q- and T-type Ca-v are present in human internal mammary arteries and in cerebral penetrating arterioles. P/Q- and T-type calcium channels are involved in the contraction of mammary arteries from hypertensive patients but not from normotensive patients. Furthermore, in cerebral arterioles P/Q-type channels importance was restricted to hypertensive patients might lead to that T-and P/Q-type channels could be a new target in hypertensive patients.