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Serum calcium and the calcium-sensing receptor polymorphism rs17251221 in relation to coronary heart disease, type 2 diabetes, cancer and mortality: the Tromsø Study

  • GENETIC EPIDEMIOLOGY
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Abstract

Serum calcium measured in 27,158 subjects in 1994 and the calcium-sensing receptor polymorphism rs17251221 genotyped in 9,404 subjects were related to cardiovascular risk factors, incident myocardial infarction (MI), type 2 diabetes (T2DM), cancer and death during follow-up until 2008–2010. In a Cox regression model with adjustment for age, gender, smoking and body mass index, subjects with serum calcium 2.50–2.60 mmol/L had a significantly increased risk of incident MI [n = 1,802, hazards ratio (HR) 1.40, 95 % confidence interval (CI) 1.18, 1.66] and T2DM (n = 705, HR 1.49, 95 % CI 1.15, 1.94) and a significantly reduced risk of cancer (n = 2,222, HR 0.73, 95 % CI 0.62, 0.86) as compared to subjects with serum calcium 2.20–2.29 mmol/L. For rs17251221 there was a mean difference in serum calcium of 0.05 mmol/L between major and minor homozygote genotypes. No consistent, significant relation between rs17251221 and risk factors or the major hard endpoints were found. The minor homozygote genotype (high serum calcium) had a significant twofold increased risk (HR 2.32, 95 % CI 1.24, 4.36) for prostate cancer, as compared to the major homozygote. This may be clinically important if confirmed in other cohorts.

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Abbreviations

BMI:

Body mass index

CASR:

Calcium-sensing receptor

CI:

Confidence intervals

CVD:

Cardiovascular disease

HbA1c :

Glycated haemoglobin

HR:

Hazard ratio

LD:

Linkage disequilibrium

MI:

Myocardial infarction

PTH:

Parathyroid hormone

SNPs:

Single nucleotide polymorphisms

T2DM:

Type 2 diabetes

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Acknowledgments

We are indebted to the National Health Screening Service for their participation in collection of data in the fourth survey of the Tromsø Study. The present study was supported by grants from The North Norway Regional Health Authority, The Norwegian Diabetes Association, The Research Council of Norway and The University of Tromsø.

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Clinical Medicine, University of Tromsø, 9038, Tromsö, Norway

    Rolf Jorde, Henrik Schirmer, Ellisiv Bøgeberg Mathiesen & Guri Grimnes

  2. Division of Internal Medicine, University Hospital of North Norway, Tromsö, Norway

    Rolf Jorde, Elena Kamycheva & Guri Grimnes

  3. Division of Cardiology, University Hospital of North Norway, Tromsö, Norway

    Henrik Schirmer

  4. Department of Community Medicine, University of Tromsø, Tromsö, Norway

    Inger Njølstad & Maja-Lisa Løchen

  5. Department of Neurology and Neurophysiology, University Hospital of North Norway, Tromsö, Norway

    Ellisiv Bøgeberg Mathiesen

  6. Faculty of Health Sciences, Institute of Medical Biology, University of Tromsø, Tromsö, Norway

    Yngve Figenschau

  7. Department of Laboratory Medicine, University Hospital of North Norway, Tromsö, Norway

    Yngve Figenschau

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  1. Rolf Jorde
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Correspondence to Rolf Jorde.

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Jorde, R., Schirmer, H., Njølstad, I. et al. Serum calcium and the calcium-sensing receptor polymorphism rs17251221 in relation to coronary heart disease, type 2 diabetes, cancer and mortality: the Tromsø Study. Eur J Epidemiol 28, 569–578 (2013). https://doi.org/10.1007/s10654-013-9822-y

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  • DOI: https://doi.org/10.1007/s10654-013-9822-y

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