Blood pressure levels in male carriers of Arg82Cys in CD300LG
Julie Støy, Niels Grarup, Arne Hørlyck, Liselotte Ibsen, Jørgen Rungby, Per Løgstrup Poulsen, Ivan Brandslund, Cramer Christensen, Torben Hansen, Oluf Pedersen, Niels Møller, Ulla Kampmann, Julie Støy, Niels Grarup, Arne Hørlyck, Liselotte Ibsen, Jørgen Rungby, Per Løgstrup Poulsen, Ivan Brandslund, Cramer Christensen, Torben Hansen, Oluf Pedersen, Niels Møller, Ulla Kampmann
Abstract
The genetics of hypertension has been scrutinized in large-scale genome-wide association studies (GWAS) with a large number of common genetic variants identified, each exerting subtle effects on disease susceptibility. An amino acid polymorphism, p.Arg82Cys, in CD300LG was recently found to be associated with fasting HDL-cholesterol and triglyceride levels. The polymorphism has not been detected in hypertension GWAS potentially due to its low frequency, but CD300LG has been linked to blood pressure as CD300LG knockout mice have changes in blood pressure. Twenty-four-hour ambulatory blood pressure was obtained in human CD300LG CT-carriers to follow up on these observations.
Methods: Twenty healthy male CD300LG rs72836561 CT-carriers matched for age and BMI with 20 healthy male CC-carriers. Office blood pressure, 24-hour ambulatory blood pressure, carotid intima-media thickness (CIMT), and fasting blood samples were evaluated. The clinical study was combined with a genetic-epidemiological study to replicate the association between blood pressure and CD300LG Arg82Cys in 2,637 men and 3,249 women.
Results: CT-carriers had a higher 24-hour ambulatory systolic blood pressure (122 mmHg versus 115; p = 0.01) and diastolic blood pressure (77 mmHg versus 72; p<0.01) compared with CC-carriers. There were no differences in CIMT between the two groups. Metalloproteinase-9 level was higher in CT-carriers than in CC-carriers (P<0.01). However, no association between office blood pressure and CD300LG genotype was detected in the genetic-epidemiological study.
Conclusions: Although 24-hour blood pressure, measured with a sensitive method, in a small sample of CD300LG rs72836561 CT-carriers was higher than in CC-carriers, this did not translate into significant differences in office blood pressure in a larger cohort. This discrepancy which may reflect differences in methodological approach, underlines the importance of performing replication studies in a larger clinical context, but a formal rejection of a relation between blood pressure and CD300LG requires measurement of 24-hour ambulatory blood pressure in a larger cohort.
Trial registration: ClinicalTrials.gov NCT01571609.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
References
- Lewington S, Clarke R, Qizilbash N, Peto R, Collins R (2002) Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 360: 1903–1913.
- Faraco G, Iadecola C (2013) Hypertension: a harbinger of stroke and dementia. Hypertension 62: 810–817.
- Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, et al. (2010) Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466: 707–713.
- Scott RA, Lagou V, Welch RP, Wheeler E, Montasser ME, et al. (2012) Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat Genet 44: 991–1005.
- Ehret GB, Munroe PB, Rice KM, Bochud M, Johnson AD, et al. (2011) Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478: 103–109.
- Randall JC, Winkler TW, Kutalik Z, Berndt SI, Jackson AU, et al. (2013) Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits. PLoS Genet 9: e1003500.
- Albrechtsen A, Grarup N, Li Y, Sparso T, Tian G, et al. (2012) Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes. Diabetologia.
- Umemoto E, Tanaka T, Kanda H, Jin S, Tohya K, et al. (2006) Nepmucin, a novel HEV sialomucin, mediates L-selectin-dependent lymphocyte rolling and promotes lymphocyte adhesion under flow. J Exp Med 203: 1603–1614.
- Jin S, Umemoto E, Tanaka T, Shimomura Y, Tohya K, et al. (2008) Nepmucin/CLM-9, an Ig domain-containing sialomucin in vascular endothelial cells, promotes lymphocyte transendothelial migration in vitro. FEBS Lett 582: 3018–3024.
- Umemoto E, Hayasaka H, Bai Z, Cai L, Yonekura S, et al. (2011) Novel regulators of lymphocyte trafficking across high endothelial venules. Crit Rev Immunol 31: 147–169.
- Takatsu H, Hase K, Ohmae M, Ohshima S, Hashimoto K, et al. (2006) CD300 antigen like family member G: A novel Ig receptor like protein exclusively expressed on capillary endothelium. Biochem Biophys Res Commun 348: 183–191.
- Cannon JP, O'Driscoll M, Litman GW (2012) Specific lipid recognition is a general feature of CD300 and TREM molecules. Immunogenetics 64: 39–47.
- Umemoto E, Takeda A, Jin S, Luo Z, Nakahogi N, et al. (2013) Dynamic changes in endothelial cell adhesion molecule nepmucin/CD300LG expression under physiological and pathological conditions. PLoS One 8: e83681.
- Mancia G, Sega R, Bravi C, De Vito G, Valagussa F, et al. (1995) Ambulatory blood pressure normality: results from the PAMELA study. J Hypertens 13: 1377–1390.
- Jeppesen JL, Nielsen SJ, Torp-Pedersen C, Hansen TW, Olsen MH, et al. (2012) Genetic variation in the natriuretic peptide system, circulating natriuretic peptide levels, and blood pressure: an ambulatory blood pressure study. Am J Hypertens 25: 1095–1100.
- Galis ZS, Khatri JJ (2002) Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ Res 90: 251–262.
- Engelen L, Ferreira I, Stehouwer CD, Boutouyrie P, Laurent S (2013) Reference intervals for common carotid intima-media thickness measured with echotracking: relation with risk factors. Eur Heart J 34: 2368–2380.
Source: PubMed