Interactions of single nucleotide polymorphisms with dietary calcium intake on the risk of metabolic syndrome

Abstract

Background: Gene-nutrient interactions may be important in modulating susceptibility to metabolic disorders. Objectives: The objectives of this study were to assess the association of dietary calcium intake with the risk of metabolic syndrome and to investigate the interaction effects between dietary calcium intake and candidate gene polymorphisms. Design: Subjects were participants in the Korea Association Resource project, which was initiated in 2007 as a large-scale, genome-wide association analysis. A total of 8031 subjects were included in the study. Associations were assessed by using multivariable-adjusted logistic regression analyses. Results: High calcium intake appeared to be associated with a low risk of metabolic syndrome after covariates in both men (P-trend = 0.03) and women (P-trend = 0.0002) were controlled for. Among 27 single nucleotide polymorphisms (SNPs) selected as possible candidate gene polymorphisms affecting the risk of metabolic syndrome, 3 SNPs [rs6445834 in Rho guanine nucleotide exchange factor 3 (ARHGEF3), rs10850335 in T-box 5 (TBX5), rs180349 in BUD13 homolog (Saccaromyces cerevisiae) (BUD13)] showed significant interaction effects with calcium intake tertiles or sufficiency in both men and women. Subjects with major allele homozygotes of these gene polymorphisms and high calcium intakes generally had a lower risk of metabolic syndrome than did those with minor allele homozygotes and low calcium intakes. Conclusion: Dietary calcium intake appears to be inversely associated with the risk of metabolic syndrome and may modulate susceptibility to the syndrome in subjects who are minor allele carriers of rs6445834 in ARHGEF3, rs10850335 in TBX5, or rs180349 in BUD13. Am J Clin Nutr 2012;95:231-40.