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.MethodsTwenty 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.ResultsCT-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.ConclusionsAlthough 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.
Highlights
Hypertension constitutes an important public health challenge due to its association with cardiovascular diseases [1,2]
No association between office blood pressure and CD300LG genotype was detected in the genetic-epidemiological study
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
Summary
Hypertension constitutes an important public health challenge due to its association with cardiovascular diseases [1,2]. Hypertension often coexists with metabolic disorders such as obesity, dyslipidaemia, and glucose intolerance. Each of these disorders has been scrutinized in genetic association studies with a large number of genetic variants identified that exert a subtle effect on disease susceptibility [3,4,5,6]. The biological functions of CD300LG are not well characterized, but CD300LG knockout (KO) mice have osteopenia and decreased systolic blood pressure (US patent number 2008/0311107A1, Bollinger et al.). Aspects of the cardiovascular phenotype were characterized in healthy male heterozygous carriers of the CD300LG rs72836561 polymorphism to address the hypothesis that CD300LG has effects on blood pressure regulation as suggested in studies of the CD300LG KO mice
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