Serum calcium and the calcium-sensing receptor polymorphism rs17251221 in relation to coronary heart disease, type 2 diabetes, cancer and mortality: the Tromsø Study
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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.
KeywordsCalcium-sensing receptor Cancer Cardiovascular disease Mortality Prostate cancer Serum calcium
Body mass index
Single nucleotide polymorphisms
Type 2 diabetes
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
- 15.Chung M, Balk EM, Brendel M, Ip S, Lau J, Lee J, Lichtenstein A, Patel K, Raman G, Tatsioni A, Terasawa T, Trikalinos TA. Vitamin D and calcium: a systematic review of health outcomes. Evid Rep Technol Assess. 2009;183:1–420.Google Scholar
- 19.Kapur K, Johnson T, Beckmann ND, Sehmi J, Tanaka T, Kutalik Z, Styrkarsdottir U, Zhang W, Marek D, Gudbjartsson DF, Milaneschi Y, Holm H, Diiorio A, Waterworth D, Li Y, Singleton AB, Bjornsdottir US, Sigurdsson G, Hernandez DG, Desilva R, Elliott P, Eyjolfsson GI, Guralnik JM, Scott J, Thorsteinsdottir U, Bandinelli S, Chambers J, Stefansson K, Waeber G, Ferrucci L, Kooner JS, Mooser V, Vollenweider P, Beckmann JS, Bochud M, Bergmann S. Genome-wide meta-analysis for serum calcium identifies significantly associated SNPs near the calcium-sensing receptor (CASR) gene. PLoS Genet. 2010;6:e1001035.PubMedCrossRefGoogle Scholar
- 20.O’Seaghdha CM, Yang Q, Glazer NL, Leak TS, Dehghan A, Smith AV, Kao WH, Lohman K, Hwang SJ, Johnson AD, Hofman A, Uitterlinden AG, Chen YD, GEFOS Consortium, Brown EM, Siscovick DS, Harris TB, Psaty BM, Coresh J, Gudnason V, Witteman JC, Liu YM, Kestenbaum BR, Fox CS, Köttgen A. Common variants in the calcium-sensing receptor gene are associated with total serum calcium levels. Hum Mol Genet. 2010;19:4296–303.PubMedCrossRefGoogle Scholar
- 22.Grimnes G, Emaus N, Joakimsen RM, Figenschau Y, Figenschau Y, Jenssen T, Njølstad I, Schirmer H, Jorde R. Baseline serum 25-hydroxyvitamin D concentrations in the Tromsø Study 1994–95 and risk of developing type 2 diabetes mellitus during 11 years of follow-up. Diabet Med. 2010;27:1107–15.PubMedCrossRefGoogle Scholar
- 23.Jorde R, Schirmer H, Wilsgaard T, Joakimsen RM, Mathiesen EB, Njølstad I, Løchen ML, Figenschau Y, Berg JP, Svartberg J, Grimnes G. Polymorphisms related to the serum 25-hydroxyvitamin D level and risk of myocardial infarction, diabetes, cancer and mortality. The Tromsø Study. PLoS One. 2012;7:e37295.PubMedCrossRefGoogle Scholar
- 25.Mannsverk J, Wilsgaard T, Njølstad I, Hopstock LA, Løchen ML, Mathiesen EB, Thelle DS, Rasmussen K, Bønaa KH. Age and gender differences in incidence and case fatality trends for myocardial infarction: a 30-year follow-up. The Tromso Study. Eur J Prev Cardiol. 2012;19:927–34.PubMedCrossRefGoogle Scholar
- 40.Raue F, Pichl J, Dörr HG, Schnabel D, Heidemann P, Hammersen G, Jaursch-Hancke C, Santen R, Schöfl C, Wabitsch M, Haag C, Schulze E, Frank-Raue K. Activating mutations in the calcium-sensing receptor: genetic and clinical spectrum in 25 patients with autosomal dominant hypocalcaemia—a German survey. Clin Endocrinol. 2011;75:760–5.CrossRefGoogle Scholar