Sex Differences in Circadian Clock Genes and Myocardial Infarction Susceptibility.
Ontology highlight
ABSTRACT:
SUBMITTER: Skrlec I
PROVIDER: S-EPMC8151899 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The circadian rhythm regulates various physiological mechanisms, and its disruption can promote many disorders. Disturbance of endogenous circadian rhythms enhances the chance of myocardial infarction (MI), showing that circadian clock genes could have a crucial function in the onset of the disease. This case-control study was performed on 1057 participants. It was hypothesized that the polymorphisms of one nucleotide (SNP) in three circadian clock genes (CLOCK, ARNTL, and PER2) could be associated with MI. Statistically significant differences, estimated by the Chi-square test, were found in the distribution of alleles and genotypes between MI and no-MI groups of the CLOCK (rs6811520 and rs13124436) and ARNTL (rs3789327 and rs12363415) genes. According to the results of the present study, the polymorphisms in the CLOCK and ARNTL genes could be related to MI.
| S-EPMC7074039 | biostudies-literature
Project description:Disruption of endogenous circadian rhythms has been shown to increase the risk of developing myocardial infarction (MI), suggesting that circadian genes might play a role in determining disease susceptibility. We conducted a case-control study on 200 patients hospitalized due to MI and 200 healthy controls, investigating the association between MI and single nucleotide polymorphisms (SNPs) in four circadian genes (ARNTL, CLOCK, CRY2, and PER2). The variants of all four genes were chosen based on their previously reported association with cardiovascular risk factors, which have a major influence on the occurrence of myocardial infarction. Statistically significant differences, assessed through Chi-square analysis, were found in genotype distribution between cases and controls of the PER2 gene rs35333999 (p=0.024) and the CRY2 gene rs2292912 (p=0.028); the corresponding unadjusted odds ratios, also significant, were respectively OR=0.49 (95% CI 0.26-0.91) and OR=0.32 (95% CI 0.11-0.89). Our data suggest that genetic variability in the CRY2 and PER2 genes might be associated with myocardial infarction.
| S-EPMC6082246 | biostudies-literature
Project description:Background Myocardial infarction is an important cause of morbidity and mortality in both men and women. Atypical or the absence of symptoms, more prevalent among women, may contribute to unrecognized myocardial infarctions and missed opportunities for preventive therapies. The aim of this research is to investigate sex-based differences of undiagnosed myocardial infarction in the general population. Methods and Results In the Lifelines Cohort Study, all individuals ≥18 years with a normal baseline ECG were followed from baseline visit till first follow-up visit (≈5 years, n=97 203). Individuals with infarct-related changes between baseline and follow-up ECGs were identified. The age- and sex-specific incidence rates were calculated and sex-specific cardiac symptoms and predictors of unrecognized myocardial infarction were determined. Follow-up ECG was available after a median of 3.8 (25th and 75th percentile: 3.0-4.6) years. During follow-up, 198 women experienced myocardial infarction (incidence rate 1.92 per 1000 persons-years) compared with 365 men (incidence rate 3.30; P<0.001 versus women). In 59 (30%) women, myocardial infarction was unrecognized compared with 60 (16%) men (P<0.001 versus women). Individuals with unrecognized myocardial infarction less often reported specific cardiac symptoms compared with individuals with recognized myocardial infarction. Predictors of unrecognized myocardial infarction were mainly hypertension, smoking, and higher blood glucose level. Conclusions A substantial proportion of myocardial infarctions are unrecognized, especially in women. Opportunities for secondary preventive therapies remain underutilized if myocardial infarction is unrecognized.
| S-EPMC7670510 | biostudies-literature
Project description:AimsInternal and external triggers affect seasonal and circadian variations of myocardial infarction (MI). We aimed to assess sex differences in the common triggers of MI.Methods and resultsA nationwide, retrospective, cross-sectional postal survey study was conducted. Individuals who experienced a MI during holidays and weekdays were identified through the SWEDEHEART registry. Twenty-seven potential MI triggers were rated in regards to occurring more or less than usual during the last 24 h before the MI. Three areas were covered: activities, emotions, and food or alcohol consumption. A logistic regression model was used to identify sex differences for each trigger and odds ratios (ORs) were reported. Four hundred and fifty-one patients, of whom 317 were men, responded. The most commonly reported triggers were stress (35.3%), worry (26.2%), depression (21.1%), and insomnia (20.0%). Women reported emotional triggers including sadness [OR 3.52, 95% confidence interval (CI) 1.92-6.45], stress (OR 2.38, 95% CI 1.52-3.71), insomnia (OR 2.31, 95% CI 1.39-3.81), and upset (OR 2.69, 95% CI 1.47-4.95) to a greater extent than men. Outdoor activity was less reported by women (OR 0.35, 95% CI 0.14-0.87). No significant sex differences were found in other activities or food and alcohol consumption.ConclusionSelf-experienced stress and distress were higher among women prior to MI compared with men. Understanding sex perspectives in acute triggers may help us find preventive strategies and reduce the excess numbers of MI.
| S-EPMC10063195 | biostudies-literature
Project description:The daily biological clock regulates the timing of sleep and physiological processes that are of fundamental importance to human health, performance, and well-being. Environmental parameters of relevance to biological clocks include (1) daily fluctuations in light intensity and temperature, and (2) seasonal changes in photoperiod (day length) and temperature; these parameters vary dramatically as a function of latitude and locale. In wide-ranging species other than humans, natural selection has genetically optimized adaptiveness along latitudinal clines. Is there evidence for selection of clock gene alleles along latitudinal/photoperiod clines in humans? A number of polymorphisms in the human clock genes Per2, Per3, Clock, and AANAT have been reported as alleles that could be subject to selection. In addition, this investigation discovered several novel polymorphisms in the human Arntl and Arntl2 genes that may have functional impact upon the expression of these clock transcriptional factors. The frequency distribution of these clock gene polymorphisms is reported for diverse populations of African Americans, European Americans, Ghanaians, Han Chinese, and Papua New Guineans (including 5 subpopulations within Papua New Guinea). There are significant differences in the frequency distribution of clock gene alleles among these populations. Population genetic analyses indicate that these differences are likely to arise from genetic drift rather than from natural selection.
| S-EPMC2579796 | biostudies-literature
Project description:Several previous studies suggest that dysfunction of circadian rhythms may increase susceptibility to bipolar disorder (BP). We conducted an association study of five circadian genes (CRY2, PER1-3, and TIMELESS) in a family collection of 36 trios and 79 quads (Sample I), and 10 circadian genes (ARNTL, ARNTL2, BHLHB2, BHLHB3, CLOCK, CRY1, CSNK1D, CSNK1E, DBP, and NR1D1) in an extended family collection of 70 trios and 237 quads (Sample II), which includes the same 114 families but not necessarily the same individuals as Sample I. In Sample II, the Sibling-Transmission Disequilibrium Test (sib-tdt) analysis showed nominally significant association of BP with three SNPs within or near the CLOCK gene (rs534654, P = 0.0097; rs6850524, P = 0.012; rs4340844, P = 0.015). In addition, SNPs in the ARNTL2, CLOCK, DBP, and TIMELESS genes and haplotypes in the ARNTL, CLOCK, CSNK1E, and TIMELESS genes showed suggestive evidence of association with several circadian phenotypes identified in BP patients. However, none of these associations reached gene-wide or experiment-wide significance after correction for multiple-testing. A multi-locus interaction between rs6442925 in the 5' upstream of BHLHB2, rs1534891 in CSNK1E, and rs534654 near the 3' end of the CLOCK gene, however, is significantly associated with BP (P = 0.00000172). It remains significant after correcting for multiple testing using the False Discovery Rate method. Our results indicate an interaction between three circadian genes in susceptibility to bipolar disorder.
| S-EPMC2574897 | biostudies-literature
Project description:BackgroundWe sought to investigate the sex differences in the effectiveness of statins in patients with acute myocardial infarction (AMI).MethodsLinking hospital discharge and drug claims databases from Quebec, Canada (1998-2004), we identified statin users (n = 14 710) and non-users (n = 23 833) discharged from hospital after an AMI-related hospital stay and followed up for as long as 7 years.ResultsAll-cause death rates were 4.1 and 14.6 per 100 person-years among users and non-users, respectively, whereas cardiac death rates were 2.2 and 7.4 per 100 person-years. For death from any cause, the adjusted hazard ratios associated with statin use in women were 0.61 (95% confidence interval [CI], 0.54-0.69) within 1 year of follow-up, 0.55 (0.48-0.63) at 1-3 years and 0.38 (0.31-0.49) at > 3 years; in men, the corresponding estimates were 0.54 (0.48-0.60), 0.48 (0.42-0.55) and 0.34 (0.30-0.39). For cardiac-related death, the adjusted hazard ratios associated with statin use in women were 0.70 (0.60-0.81) within 1 year, 0.56 (0.46-0.68) at 1-3 years and 0.44 (0.31-0.62) at > 3 years of follow-up, whereas in men, the estimates were 0.59 (0.51-0.69), 0.47 (0.39-0.58) and 0.37 (0.30-0.45), respectively.InterpretationStatin therapy after an AMI was associated with reduced rates of all-cause and cardiac mortality. The effect increased with time in both sexes, but the degree of risk reduction was less for women than for men.
| S-EPMC1780088 | biostudies-literature
Project description:BackgroundThe diagnosis of acute myocardial infarction (AMI) is missed more frequently in young women than men, which may be related to the cognitive psychology of the diagnostic process. Physicians start the diagnostic process by intuitively recognizing familiar symptom phenotypes, but little is known about how symptoms combine in individuals as unique symptom phenotypes. We examined how symptoms of AMI combine as unique symptom phenotypes in individual patients to compare the distribution of symptom phenotypes in women versus men.Methods and resultsThe VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) was a multicenter, observational cohort study of 3501 young adults hospitalized with AMI. Data were collected on presenting symptoms with standardized interviews and from medical record abstraction. The number and distribution of unique symptom phenotypes were compared between women and men. Because of the 2:1 female-to-male enrollment ratio, women and men were compared with permutation testing and repeated subsampling. There were 426 interview-symptom phenotypes in women and 280 in men. The observed difference between women and men of 146 phenotypes was significant, even allowing for the greater enrollment of women (permutation P=0.004, median difference 110 under the null hypothesis of no association between sex and phenotype). The repeated subsample analysis also showed significantly more interview-symptom phenotypes in women than men (206.8±7.3 versus 188.6±6.0, P<0.001). Women were more broadly distributed among symptom phenotype subgroups than men (P<0.001). Similar findings were observed in the analysis of symptoms abstracted from the medical record.ConclusionsWomen exhibited substantially more variation in unique symptom phenotypes than men, regardless of whether the symptoms were derived from structured interviews or abstracted from the medical record. These findings may provide an explanation for the higher missed diagnosis rate in young women with AMI and may have important implications for teaching and improving clinicians' ability to recognize the diagnosis of AMI in women.
| S-EPMC7041412 | biostudies-literature
Project description:BackgroundWhether sex differences exist in the inflammatory response after ST-elevation myocardial infarction (STEMI) remains to be elucidated. We studied leukocyte profiles and their prognostic value in men and women presenting with STEMI.MethodsFrom a total of 552 consecutive STEMI patients, blood samples were collected at hospital admission. Linear regression was used to assess the relationship between leukocyte profiles and enzymatic infarct size. Cox regression was used to assess the association between leukocyte profiles and one-year mortality.ResultsWomen presented with higher lymphocyte counts (2.3·109 cells/L (IQR 1.6-3.1) vs. 1.8·109 cells/L (IQR 1.4-2.5), p = 3.00 ∙ 10-4) and percentages (21.1% (IQR 14.4-28.1) vs. 17.1% (IQR 12.3-24.3), p = 0.004). Lymphocyte to monocyte ratio (LMR) was also higher in women (3.25 (IQR 2.56-4.5) vs. 2.68 (IQR 2.08-3.59), p = 7.28 ∙ 10-7). Higher LMR was associated with lower peak CK-MB (β = -0.27 (95% CI: -0.50, -0.03), p = 0.026), lower peak troponin T (β = -0.45 (95% CI: -0.77, -0.13), p = 0.006) and lower one-year mortality risk (HR 0.35 (95% CI: 0.13, 0.96), p = 0.042).ConclusionAt admission for STEMI, women present with higher lymphocyte count and LMR. Higher LMR is associated with smaller infarct size and decreased one-year mortality risk and could be used as a biomarker to predict outcome.
| S-EPMC7176674 | biostudies-literature
Project description:Background Evidence on the impact of sex on prognoses after myocardial infarction (MI) among older adults is limited. We evaluated sex differences in long-term cardiovascular outcomes after MI in older adults. Methods and Results All patients with MI ≥70 years admitted to 20 Finnish hospitals during a 10-year period and discharged alive were studied retrospectively using a combination of national registries (n=31 578, 51% men, mean age 79). The primary outcome was combined major adverse cardiovascular event within 10-year follow-up. Sex differences in baseline features were equalized using inverse probability weighting adjustment. Women were older, with different comorbidity profiles and rarer ST-segment-elevation MI and revascularization, compared with men. Adenosine diphosphate inhibitors, anticoagulation, statins, and high-dose statins were more frequently used by men, and renin-angiotensin-aldosterone inhibitors and beta blockers by women. After balancing these differences by inverse probability weighting, the cumulative 10-year incidence of major adverse cardiovascular events was 67.7% in men, 62.0% in women (hazard ratio [HR], 1.17; CI, 1.13-1.21; P<0.0001). New MI (37.0% in men, 33.1% in women; HR, 1.16; P<0.0001), ischemic stroke (21.1% versus 19.5%; HR, 1.10; P=0.004), and cardiovascular death (56.0% versus 51.1%; HR, 1.18; P<0.0001) were more frequent in men during long-term follow-up after MI. Sex differences in major adverse cardiovascular events were similar in subgroups of revascularized and non-revascularized patients, and in patients 70 to 79 and ≥80 years. Conclusions Older men had higher long-term risk of major adverse cardiovascular events after MI, compared with older women with similar baseline features and evidence-based medications. Our results highlight the importance of accounting for confounding factors when studying sex differences in cardiovascular outcomes.
| S-EPMC9075375 | biostudies-literature