CRY1 and CRY2 genetic variants in seasonality : A longitudinal and cross-sectional study

Cryptochromes are key components of the circadian clocks that generate and maintain seasonal variations. The aim of our study was to analyze the associations of CRY1 and CRY2 genetic variants with the problematicity of seasonal variations, and whether the problematicity of seasonal variations changed during the follow-up of 11 years. Altogether 21 CRY1 and 16 CRY2 single-nucleotide polymorphisms (SNPs) were genotyped and analyzed in 5910 individuals from a Finnish nationwide population-based sample who had filled in the self-report on the seasonal variations in mood and behavior in the year 2000. In the year 2011, 3356 of these individuals filled in the same self-report on the seasonal variations in mood and behavior. Regression models were used to test whether any of the SNPs associated with the problematicity of seasonal variations or with a change in the problematicity from 2000 to 2011. In the longitudinal analysis, CRY2 SNP rs61884508 was protective from worsening of problematicity of seasonal variations. In the cross-sectional analysis, CRY2 SNP rs72902437 showed evidence of association with problematicity of seasonal variations, as did SNP rs1554338 (in the MAPK8IP1 and downstream of CRY2). (C) 2016 Elsevier Ireland Ltd. All rights reserved.Peer reviewe

PRKCDBP (CAVIN3) and CRY2 associate with major depressive disorder

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SIRT1 Polymorphisms Associate with Seasonal Weight Variation, Depressive Disorders, and Diastolic Blood Pressure in the General Population

SIRT1 polymorphisms have previously been associated with depressive and anxiety disorders. We aimed at confirming these earlier findings and extending the analyses to seasonal variations in mood and behavior. Three tag single-nucleotide polymorphisms (SNPs) were selected to capture the common variation in the SIRT1 gene. 5910 individuals (with blood sample, diagnostic interview, self-report of on seasonal changes in mood and behavior) were selected from a representative Finnish nationwide population-based sample. Logistic and linear regression models were used to analyze the associations between the SNPs and depressive and anxiety disorders, metabolic syndrome (EGIR criteria) and its components, and health examination measurements, Homeostasis Model Assessments, and diagnoses of type 2 and type 1 diabetes. SIRT1 rs2273773 showed evidence of association with seasonal variation in weight (C-allele, OR = 0.85, 95% CI = 0.76-0.95, p = 0.005). In addition, our study gave further support for the association of SIRT1 gene with depressive disorders (rs3758391) and diastolic blood pressure (rs2273773).Peer reviewe

CLOCK is suggested to associate with comorbid alcohol use and depressive disorders

<p>Abstract</p> <p>Background</p> <p>Depression and alcohol abuse or dependence (AUD) co-occur in the general population more frequently than expected by chance. Alcohol use influences the circadian rhythms generated by the central pacemaker in the suprachiasmatic nucleus, and circadian rhythm alterations in turn are common in depressive disorders as well as among persons addicted to alcohol.</p> <p>Methods</p> <p>32 SNPs in 19 circadian clockwork related genes were analyzed using DNA from 76 individuals with comorbid depression and AUD, 446 individuals with AUD and 517 healthy controls with no psychiatric diagnosis. The individuals participated in a nationwide health examination study, representative of the general population aged 30 and over in Finland.</p> <p>Results</p> <p>The <it>CLOCK </it>haplotype TTGC formed by SNPs rs3805151, rs2412648, rs11240 and rs2412646, was associated with increased risk for comorbidity (OR = 1.65, 95% CI = 1.14-2.28, P = 0.0077). The SNPs of importance for this suggestive association were rs2412646 and rs11240 indicating location of the functional variation in the block downstream rs2412648. There was no indication for association between <it>CLOCK </it>and AUD.</p> <p>Conclusion</p> <p>Our findings suggest an association between the <it>CLOCK </it>gene and the comorbid condition of alcohol use and depressive disorders. Together with previous reports it indicates that the <it>CLOCK </it>variations we found here may be a vulnerability factor to depression given the exposure to alcohol in individuals having AUD.</p

SNP Analysis of Caries and Initial Caries in Finnish Adolescents

Background. Dental caries is the most common infection in the world and is influenced by genetic and environmental factors. Environmental factors are largely known, but the role of genetic factors is quite unknown. The aim was to investigate the genetic background of caries in Finnish adolescents. Materials and Methods. This study was carried out at the Kotka Health Center in Eastern Finland. 94 participants aged 15-17 years gave approval for the saliva and DNA analyses. However, one was excluded in DNA analysis; thus, the overall number of participants in analysis was 93. Caries status was recorded clinically and from bite-wing X-rays to all 94 participants. Genomic DNA was extracted by genomic QIAamp (R) DNA Blood Mini Kit and genotyped for polymorphisms. The results were analyzed using additive and logistic regression models. Results. No significant associations between caries and the genes studied were found. However, SNPs in DDX39B and MPO showed association tendencies but were not statistically significant after false discovery rate (FDR) analysis. SNPs in VDR, LTA, and MMP3 were not statistically significant with initial caries lesions after FDR analysis. Conclusion. The present study could not demonstrate statistically significant associations between caries and the genes studied. Further studies with larger populations are needed.Peer reviewe

NPAS2 and PER2 are linked to risk factors of the metabolic syndrome

<p>Abstract</p> <p>Background</p> <p>Mammalian circadian clocks control multiple physiological events. The principal circadian clock generates seasonal variations in behavior as well. Seasonality elevates the risk for metabolic syndrome, and evidence suggests that disruption of the clockwork can lead to alterations in metabolism. Our aim was to analyze whether circadian clock polymorphisms contribute to seasonal variations in behavior and to the metabolic syndrome.</p> <p>Methods</p> <p>We genotyped 39 single-nucleotide polymorphisms (SNP) from 19 genes which were either canonical circadian clock genes or genes related to the circadian clockwork from 517 individuals drawn from a nationwide population-based sample. Associations between these SNPs and seasonality, metabolic syndrome and its risk factors were analyzed using regression analysis. The p-values were corrected for multiple testing.</p> <p>Results</p> <p>Our findings link circadian gene variants to the risk factors of the metabolic syndrome, since <it>Npas2 </it>was associated with hypertension (P-value corrected for multiple testing = 0.0024) and <it>Per2 </it>was associated with high fasting blood glucose (P-value corrected for multiple testing = 0.049).</p> <p>Conclusion</p> <p>Our findings support the view that relevant relationships between circadian clocks and the metabolic syndrome in humans exist.</p

ARNTL (BMAL1) and NPAS2 Gene Variants Contribute to Fertility and Seasonality

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CRY2 Genetic Variants Associate with Dysthymia

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STAT3 Mutation Is Associated with STAT3 Activation in CD30+ ALK− ALCL

Peripheral T-cell lymphomas (PTCL) are a heterogeneous, and often aggressive group of non-Hodgkin lymphomas. Recent advances in the molecular and genetic characterization of PTCLs have helped to delineate differences and similarities between the various subtypes, and the JAK/STAT pathway has been found to play an important oncogenic role. Here, we aimed to characterize the JAK/STAT pathway in PTCL subtypes and investigate whether the activation of the pathway correlates with the frequency of STAT gene mutations. Patient samples from AITL (n = 30), ALCL (n = 21) and PTCL-NOS (n = 12) cases were sequenced for STAT3, STAT5B, JAK1, JAK3, and RHOA mutations using amplicon sequencing and stained immunohistochemically for pSTAT3, pMAPK, and pAKT. We discovered STAT3 mutations in 13% of AITL, 13% of ALK+ ALCL, 38% of ALK− ALCL and 17% of PTCL-NOS cases. However, no STAT5B mutations were found and JAK mutations were only present in ALK- ALCL (15%). Concurrent mutations were found in all subgroups except ALK+ ALCL where STAT3 mutations were always seen alone. High pY-STAT3 expression was observed especially in AITL and ALCL samples. When studying JAK-STAT pathway mutations, pY-STAT3 expression was highest in PTCLs harboring either JAK1 or STAT3 mutations and CD30+ phenotype representing primarily ALK− ALCLs. Further investigation is needed to elucidate the molecular mechanisms of JAK-STAT pathway activation in PTCL