Significant Sex Differences In Prevalence Research Articles

Sex-Biased Expression and Response of microRNAs in Neurological Diseases and Neurotrauma.

Neurological diseases and neurotrauma manifest significant sex differences in prevalence, progression, outcome, and therapeutic responses. Genetic predisposition, sex hormones, inflammation, and environmental exposures are among many physiological and pathological factors that impact the sex disparity in neurological diseases. MicroRNAs (miRNAs) are a powerful class of gene expression regulator that are extensively involved in mediating biological pathways. Emerging evidence demonstrates that miRNAs play a crucial role in the sex dimorphism observed in various human diseases, including neurological diseases. Understanding the sex differences in miRNA expression and response is believed to have important implications for assessing the risk of neurological disease, defining therapeutic intervention strategies, and advancing both basic research and clinical investigations. However, there is limited research exploring the extent to which miRNAs contribute to the sex disparities observed in various neurological diseases. Here, we review the current state of knowledge related to the sexual dimorphism in miRNAs in neurological diseases and neurotrauma research. We also discuss how sex chromosomes may contribute to the miRNA sexual dimorphism phenomenon. We attempt to emphasize the significance of sexual dimorphism in miRNA biology in human diseases and to advocate a gender/sex-balanced science.

Sex Differences in Aortopathy and Valve Diseases Among Patients Undergoing Cardiac Surgical Procedure

BackgroundWe aimed to study sex differences in aortopathy and valve disease among patients undergoing aortic valve replacement and/or surgical procedure for ascending aortic aneurysm and assess whether differences are specific for patients with bicuspid aortic valve (BAV) compared with patients with tricuspid aortic valve. MethodsWe used a single-center and observational cohort including 1045 patients undergoing elective open heart surgical procedure for aortic valve disease and/or ascending aortic aneurysm at the Karolinska Hospital (Stockholm, Sweden). ResultsWomen (33.0%) were older than men (mean [SD]; 67.9 [11] years vs 62.5 [13] years for men; P < .001). No significant sex difference in prevalence of ascending aortic aneurysm was found according to absolute measures (P = .19); however, women had a greater dilation of the ascending aorta when normalized for body surface area (mean, 21.8 [SD, 6.3] mm/m2 vs 19.3 [SD, 4.4] mm/m2 for men; P < .001). Among the 560 patients with BAV, women had significantly more aortic stenosis (adjusted odds ratio, 2.23; 95% CI, 1.19-4.20; P = .013) and less aortic insufficiency (adjusted odds ratio, 0.42; 95% CI, 0.23-0.78; P < .01); whereas no sex difference was found among patients with tricuspid aortic valve. ConclusionsIn this large study of patients undergoing cardiac surgical procedure, we found a greater degree of aortic dilation in women compared with men, suggesting a need for earlier monitoring of women. Moreover, women with BAV had a significantly higher prevalence of aortic stenosis compared with men. These results describe the aorta and valvular characteristics of patients by sex and provide guidance regarding which patients might benefit from closer surveillance.

Sex Differences of the Diabetic Heart.

Type 2 diabetes is a chronic disease associated with micro- and macro-vascular complications, including myocardial ischemia, and also with a specific and intrinsic cardiac dysfunction called diabetic cardiomyopathy (DCM). Both clinical and animal studies demonstrate significant sex differences in prevalence, pathophysiology, and outcomes of cardiovascular diseases (CVDs), including those associated with diabetes. The increased risk of CVDs with diabetes is higher in women compared to men with 50% higher risk of coronary artery diseases and increased mortality when exposed to acute myocardial infarction. Clinical studies also reveal a sexual dimorphism in the incidence and outcomes of DCM. Based on these clinical findings, growing experimental research was initiated to understand the impact of sex on CVDs associated with diabetes and to identify the molecular mechanisms involved. Endothelial dysfunction, atherosclerosis, coagulation, and fibrosis are mechanisms found to be sex-differentially modulated in the diabetic cardiovascular system. Recently, impairment of energy metabolism also emerged as a determinant of multiple CVDs associated with diabetes. Therefore, future studies should thoroughly analyze the sex-specific metabolic determinants to propose new therapeutic targets. With current medicine tending toward more personalized care of patients, we finally propose to discuss the importance of sex as determinant in the treatment of diabetes-associated cardiac diseases to promote a more systemic inclusion of both males and females in clinical and preclinical studies.

The Influence of Dihydrotestosterone on the Development of Graves' Disease in Female BALB/c Mice

Graves' disease (GD) is a common organ-specific autoimmune disease characterized by hyperthyroidism that has significant sex differences in prevalence and clinical expressions. Abnormal cytokine production and T cell activation may result in various manifestations of GD. Studies have shown that androgen treatment can provide protection against autoimmune diseases, but the effects of androgen treatment on GD are still unknown. Therefore, this study investigated whether a potent bioactive androgen, 5α-dihydrotestosterone (DHT), could be of benefit in a BALB/c mouse model of GD. The aims of this study were to investigate (i) whether DHT pretreatment inhibits autoimmune responses, and (ii) the mechanism of immune protection of DHT in GD. Female BALB/c mice were immunized three times with an adenovirus expressing the human thyrotropin receptor (TSHR) A-subunit (Ad-TSHR289). Three doses (1.5, 5, and 15 mg) of DHT or a matching placebo were implanted a week before the first immunization. Four weeks after the third immunization, mice were sacrificed, and blood, the spleen, and the thyroid were removed for further analysis. After DHT treatment, thyroid hormones were dramatically reduced compared with placebo. In addition, a remarkable reduction in interferon-γ and interleukin-2 production was observed in DHT-pretreated mice. DHT can alleviate the severity of GD by downregulating pro-autoimmune T helper 1 cells in female BALB/c mice. The protective influence was more noticeable with 5 mg and 15 mg doses of DHT.

Male-biased autosomal effect of 16p13.11 copy number variation in neurodevelopmental disorders.

Copy number variants (CNVs) at chromosome 16p13.11 have been associated with a range of neurodevelopmental disorders including autism, ADHD, intellectual disability and schizophrenia. Significant sex differences in prevalence, course and severity have been described for a number of these conditions but the biological and environmental factors underlying such sex-specific features remain unclear. We tested the burden and the possible sex-biased effect of CNVs at 16p13.11 in a sample of 10,397 individuals with a range of neurodevelopmental conditions, clinically referred for array comparative genomic hybridisation (aCGH); cases were compared with 11,277 controls. In order to identify candidate phenotype-associated genes, we performed an interval-based analysis and investigated the presence of ohnologs at 16p13.11; finally, we searched the DECIPHER database for previously identified 16p13.11 copy number variants. In the clinical referral series, we identified 46 cases with CNVs of variable size at 16p13.11, including 28 duplications and 18 deletions. Patients were referred for various phenotypes, including developmental delay, autism, speech delay, learning difficulties, behavioural problems, epilepsy, microcephaly and physical dysmorphisms. CNVs at 16p13.11 were also present in 17 controls. Association analysis revealed an excess of CNVs in cases compared with controls (OR = 2.59; p = 0.0005), and a sex-biased effect, with a significant enrichment of CNVs only in the male subgroup of cases (OR = 5.62; p = 0.0002), but not in females (OR = 1.19, p = 0.673). The same pattern of results was also observed in the DECIPHER sample. Interval-based analysis showed a significant enrichment of case CNVs containing interval II (OR = 2.59; p = 0.0005), located in the 0.83 Mb genomic region between 15.49–16.32 Mb, and encompassing the four ohnologs NDE1, MYH11, ABCC1 and ABCC6. Our data confirm that duplications and deletions at 16p13.11 represent incompletely penetrant pathogenic mutations that predispose to a range of neurodevelopmental disorders, and suggest a sex-limited effect on the penetrance of the pathological phenotypes at the 16p13.11 locus.

Facet Orientation and Tropism

Cross-sectional study. To evaluate the association between lumbar spine facet joint orientation, facet joint tropism, and spondylolysis identified by multidetector computed tomography (CT) in the community-based Framingham Heart Study. The association between lumbar spondylolysis and facet orientation and tropism remains unclear. This study was an ancillary project to the Framingham Heart Study. Three thousand five hundred twenty-nine participants of the Framingham Heart Study aged 40 to 80 years underwent multidetector CT imaging to assess aortic calcification. One hundred ninety-one subjects were included in this ancillary study. Facet joint features and spondylolysis were evaluated on CT scans. The final analyzed sample included 104 men with mean age 51.90+/-11.25 years and 84 women with mean age 53.61+/-10.20 years. The association between spondylolysis and facet orientation and tropism was examined using univariate and multivariate analyses. Spondylolysis was prevalent in 11.5% of the total population. chi2 test demonstrated a significant sex difference in prevalence of spondylolysis (P=0.0154), with almost 3 times higher prevalence among men. There was no statistically significant difference in facet orientation and continuous facet tropism between individuals with and without spondylolysis at the L5 level (P=0.49 to 0.91). After adjustment for age, sex, and body mass index, no significant association between the occurrence of spondylolysis and facet orientation and tropism was found. In the studied sample the prevalence of facet joint osteoarthritis was significantly higher in individuals with spondylolysis than in those without spondylolysis at both sides of L4-L5 spinal level (P=0.044 at the right side and P=0.003 at the left side) and at left side of L5-S1 level (P=0.038). We did not find an association between facet orientation, facet tropism, and spondylolysis. One of the possible explanations for this is that the high prevalence of facet joint osteoarthritis in individuals with spondylolysis in the studied sample might have led to diminished differences in facet orientation.

Women Have a Lower Prevalence of Structural Heart Disease as a Precursor to Sudden Cardiac Arrest: The Ore-SUDS (Oregon Sudden Unexpected Death Study)

Our aim was to utilize a community-based approach to identify sex-related differences in risk factors for sudden cardiac arrest (SCA). There are significant sex-based differences in prevalence and manifestation of SCA. Any differences related to predictors of SCA in women versus men are likely to have implications for risk stratification and prevention. The Ore-SUDS (Oregon Sudden Unexpected Death Study) is an ongoing prospective investigation of SCA in the Portland, Oregon, metropolitan area (population approximately 1 million). All cases meeting criteria for SCA were ascertained using multiple sources. Medical records were reviewed to identify clinical conditions that may contribute to SCA risk, and comparisons were made between male and female SCA cases using Pearson's chi-square tests for categorical variables, t tests for continuous variables, and multivariate logistic regression analysis. During 2002 to 2007, 1,568 adult SCA cases were identified (women 36% vs. men 64%; p < 0.0001) and women were older (mean age 71 +/- 14 years vs. 65 +/- 14 years, p < 0.0001). There were no significant sex differences in prevalence of obesity, dyslipidemia, history of chronic obstructive pulmonary disease/asthma, left ventricular (LV) hypertrophy, or history of myocardial infarction. In multivariate analysis, women were significantly less likely to have severe LV dysfunction (odds ratio: 0.51; 95% confidence interval: 0.31 to 0.84) or previously recognized coronary artery disease (odds ratio: 0.34; 95% confidence interval: 0.20 to 0.60) compared with men. Women were significantly less likely than men to have a diagnosis of structural heart disease (LV dysfunction or coronary artery disease) before SCA. These findings suggest that fewer women may be eligible for prophylactic implantable cardioverter-defibrillator placement based on current guidelines and therefore may not have equal opportunity for prevention. Enhancement of SCA risk stratification may have even higher importance for women.

Prevalence and Associations of Retinal Vein Occlusion in Australia

To determine the prevalence and associations of retinal vein occlusion (RVO) in a defined older Australian population. Participants (N = 3654; age, > or = 49 years), representing 88% of the permanent residents from an area west of Sydney, Australia, underwent a detailed eye examination, including stereophotography (Zeiss). The diagnosis of RVO was made clinically and from photographic grading. Signs of RVO were found in 59 participants (1.6%; 95% confidence interval, 1.3-1.9). The prevalence for each age-specific participant was as follows: 0.7%, younger than 60 years; 1.2%, 60 to 69 years; 2.1%, 70 to 79 years; and 4.6%, 80 years or older. There was no significant sex difference in prevalence. Branch RVO was observed in 41 subjects (69.5%); of this number, 10 subjects had branch RVO outside the vascular arcade or in the nasal fundus and 3 subjects developed new vessels. Hemispheric RVO was found in 3 subjects (5.1%), and central RVO was observed in 15 (25%); RVO was bilateral in 3 subjects (5.1%). Visual acuity was affected most in the people with central RVO, with a visual acuity of 20/200 or less in 60% compared with 14% among the people with branch RVO. Retinal vein occlusion was the fifth most frequent cause of unilateral blindness in this population. Significant associations with RVO were found with glaucoma, hypertension, stroke, and angina. This study emphasizes RVO as an important cause of unilateral visual loss in an older population. The proportion of the 3 vein occlusion sites shows some differences from those of clinic-based reports and suggests a likely selection bias in previous clinic studies.