Objective: Previous studies have suggested various causes of restless legs syndrome (RLS), including iron and dopamine concentrations in the brain. Genetic influences have also been reported in many studies. There is also a possibility that circadian clock genes may be involved because symptoms of RLS worsen at night. We investigated whether CLOCK and NPAS2 gene polymorphisms were associated with RLS. Methods: A total of 227 patients with RLS and 229 non-RLS matched controls were assessed according to the International Restless Legs Syndrome Study Group diagnostic criteria. Genotyping was performed using reverse transcription polymerase chain reaction and high-resolution melting curve analyses. Results: Although the genotype distributions of the CLOCK variants (rs1801260 and rs2412646) were not significantly different between patients with RLS and non-RLS controls, the allele frequencies of CLOCK rs1801260 showed marginally significant differences between the two groups (X2 =2.98, p=0.085). Furthermore, there was a significant difference in the distribution of CLOCK haplotypes (rs1801260-rs2412646) between patients with RLS and non-RLS controls (p=0.013). The distributions of allelic, genotypic, and haplotypic variants of NPAS2 (rs2305160 and rs6725296) were not significantly different between the two groups. Conclusion Our results suggest that CLOCK variants may be associated with decreased susceptibility to RLS.

Objective: Evidence for the association between circadian rhythm delay and depression is accumulating. Genetic studies have shown that certain polymorphisms in circadian genes are potential genetic markers of diurnal preference. Along with circadian genes, there is a growing interest in other genetic effects on circadian rhythms. This study evaluated whether the HTR2A rs6311 (-1438C/T) polymorphism is associated with diurnal preference in a Korean population. Methods: A total of 510 healthy subjects were included in this study. All subjects were genotyped for the HTR2A rs6311 polymorphism and they completed the Korean version of the composite scale of morningness (CSM). Results: The C allele carriers (C/C+C/T) showed significantly higher CSM scores compared to C allele non-carriers (T/T) (t=2.22, p= 0.03), suggesting the existence of a morning chronotype tendency in C allele carriers. In other words, the T/T genotype may be associated with the evening chronotype. Conclusion These results suggest that the HTR2A rs6311 polymorphism may be associated with diurnal preference in a healthy Korean population. The absence of the C allele may be responsible for the increasing susceptibility to eveningness in the Korean population. Further studies on HTR2A polymorphisms that evaluate their interactions with various candidate genes and differences in phenotypic expression of polymorphisms according to ethnic groups are warranted to fully understand their association with diurnal preference.

Background: Perioperative adverse cardiac events (PACE), a composite of myocardial infarction, coronary revascularization, congestive heart failure, arrhythmic attack, acute pulmonary embolism, cardiac arrest, and stroke during 30-day postoperative period, is associated with long-term mortality, but with limited clinical evidence. We compared long-term mortality with PACE using data from nationwide multicenter electronic health records. Methods: Data from 7 hospitals, converted to Observational Medical Outcomes Partnership Common Data Model, were used. We extracted records of 277,787 adult patients over 18 years old undergoing non-cardiac surgery for the first time at the hospital and had medical records for more than 180 days before surgery. We performed propensity score matching and then an aggregated meta‑analysis. Results: After 1:4 propensity score matching, 7,970 patients with PACE and 28,807 patients without PACE were matched. The meta‑analysis showed that PACE was associated with higher one-year mortality risk (hazard ratio [HR]: 1.33, 95% CI [1.10, 1.60], P = 0.005) and higher three-year mortality (HR: 1.18, 95% CI [1.01, 1.38], P = 0.038). In subgroup analysis, the risk of one-year mortality by PACE became greater with higher-risk surgical procedures (HR: 1.20, 95% CI [1.04, 1.39], P = 0.020 for low-risk surgery; HR: 1.69, 95% CI [1.45, 1.96], P < 0.001 for intermediate-risk; and HR: 2.38, 95% CI [1.47, 3.86], P = 0.034 for high-risk). Conclusions A nationwide multicenter study showed that PACE was significantly associated with increased one-year mortality. This association was stronger in high-risk surgery, older, male, and chronic kidney disease subgroups. Further studies to improve mortality associated with PACE are needed.