CRY1, CRY2 and PRKCDBP genetic variants in metabolic syndrome.
The circadian clock affects metabolic cycles, and there is a link between circadian clock genes and metabolic syndrome. Therefore, we wanted to investigate whether variants of the core circadian clock genes, cryptochrome circadian clocks 1 and 2 (CRY1 and CRY2), or those of protein kinase C, delta binding protein (PRKCDBP), which regulate the interactions and abundance of dimers of the period and cryptochrome proteins, are associated with metabolic syndrome or its components. The association of 48 single-nucleotide polymorphisms (SNPs) from CRY1, CRY2 and PRKCDBP genes with metabolic disorder or its components was analyzed in a sample of 5910 individuals. Genotyping was performed using the Sequenom MassARRAY system. SNPs and haplotypes were analyzed using linear or logistic regression with additive models controlling for age and sex. Continuous phenotypes were permuted 10,000 times. False discovery rate q-values were calculated to correct for multiple testing. Overall, CRY1 and CRY2 variants showed nominal association with the metabolic syndrome components, hypertension and triglyceride levels, and one CRY2 variant had an association with metabolic syndrome, although none of these associations yielded significant q-values. However, the haplotype analysis of these variants supported the association of CRY1 with arterial hypertension and elevated blood pressure. Further studies are warranted regarding the role of CRY1 in cardiovascular diseases.
Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare (THL), Helsinki, Finland.
Leena
L
Kovanen
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Kati
K
Donner
1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland [2] Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
Mari
M
Kaunisto
Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare (THL), Helsinki, Finland.
Timo
T
Partonen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056931:Cryptochromes / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
C505360:CAVIN3 protein, human; C538963:CRY1 protein, human; C538966:CRY2 protein, human; D056931:Cryptochromes; D047908:Intracellular Signaling Peptides and Proteins