The importance of having two X chromosomes

Arnold, Arthur P.; Reue, Karen; Eghbali, Mansoureh; Vilain, Éric; Chen, Xuqi; Ghahramani, Negar; Itoh, Yuichiro; Li, Jingyuan; Link, Jenny; Ngun, Tuck C; Williams-Burris, Shayna M.

doi:10.1098/rstb.2015.0113

Cited by 99 publications

(67 citation statements)

References 105 publications

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“…In addition to gonadal hormones, sex chromosome complement could contribute to sex differences in metabolic traits (8, 69). It has been difficult to address whether hormone-independent effects of gonadal sex occur in humans because, typically, XX chromosomes and ovaries occur together, and XY chromosomes and testes occur together (Figure 2).…”

Section: Sex and Metabolismmentioning

confidence: 99%

Genetic Basis for Sex Differences in Obesity and Lipid Metabolism

2017

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Men and women exhibit significant differences in obesity, cardiovascular disease and diabetes. To provide better diagnosis and treatment for both sexes, it is important to identify factors that underlie the observed sex differences. Traditionally, sex differences have been attributed to the differential effects of male and female gonadal secretions (commonly referred to as “sex hormones”), which do substantially influence many aspects of metabolism and related diseases. Less appreciated as a contributor to sex differences are the fundamental genetic differences between males and females, which are ultimately determined by the presence of an XX or XY sex chromosome complement. Here we review the mechanisms by which gonadal hormones and sex chromosome complement each contribute to lipid metabolism and associated diseases, and the current approaches that are used to study them. We focus particularly on genetic approaches including genome-wide association studies in humans and mice, “–omics” and “systems genetics” approaches, and unique experimental mouse models that allow distinction between gonadal and sex chromosome effects.

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Section: Sex and Metabolismmentioning

confidence: 99%

Genetic Basis for Sex Differences in Obesity and Lipid Metabolism

2017

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“…In this issue, Arnold and co-workers [47] report on the use of novel mouse models in which the number of X chromosomes is emancipated from either gonadal sex or the presence of a Y chromosome. The fourcore-genotype model allows for comparison of XX individuals with ovaries and testis and XY individuals with ovaries and testes.…”

Section: Animal Studies Inform Humans About Humansmentioning

confidence: 99%

Multifaceted origins of sex differences in the brain

McCarthy

2016

Phil. Trans. R. Soc. B

150

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Studies of sex differences in the brain range from reductionistic cell and molecular analyses in animal models to functional imaging in awake human subjects, with many other levels in between. Interpretations and conclusions about the importance of particular differences often vary with differing levels of analyses and can lead to discord and dissent. In the past two decades, the range of neurobiological, psychological and psychiatric endpoints found to differ between males and females has expanded beyond reproduction into every aspect of the healthy and diseased brain, and thereby demands our attention. A greater understanding of all aspects of neural functioning will only be achieved by incorporating sex as a biological variable. The goal of this review is to highlight the current state of the art of the discipline of sex differences research with an emphasis on the brain and to contextualize the articles appearing in the accompanying special issue.

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“…In fact, there is growing evidence that many genes are expressed/function in a “sexually dimorphic manner” [36–38]. Sex has been found to be an important modifying factor in HCM phenotype.…”

Section: Discussionmentioning

confidence: 99%

Sex-related differences in the associations between plasma free fatty acid levels and clinical features in patients with hypertrophic cardiomyopathy

et al. 2016

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BackgroundPrevious studies have indicated that inefficient energy utilization may play a pivotal role in hypertrophic cardiomyopathy (HCM). However, whether plasma free fatty acid (FFA), a main energy substrate of heart, has an effect on HCM remains unclear. Besides, several studies have suggested sex-related differences in HCM features and FFA metabolism. Here, we aimed to explore the association between plasma FFA levels and HCM and potential effects of sex on this relation.MethodsA total of 412 patients (age 47.8 ± 12.7 years, 243 males (59.0%)) with HCM were recruited. Complete medical history was collected. Echocardiography and cardiovascular magnetic resonance imaging (CMRI) were performed. Fasting plasma FFA was determined by clinical laboratory. Left ventricular mass (LVM), maximum wall thickness (MWT), and left atrium diameter (LAD) were assessed with CMRI.ResultsThe median FFA levels were 0.38 (interquartile range (IQR) 0.27–0.52) mmol/L in men and 0.40 (IQR 0.30–0.59) mmol/L in women. The FFA levels were significantly lower in men compared with those in women (p = 0.005). Compared with women, men had greater LVM index (LVMI) (96.8 ± 37.6 vs. 78.6 ± 31.5 g/m2, p < 0.001). FFA levels in male patients correlated positively with LVM, LVMI, LAD, cholesterol levels, high-density lipoprotein-cholesterol (HDL-C) levels, heart rate, and systolic blood pressure (SBP). However, none of these variables were significantly associated with sqrt (FFA) in female patients except a borderline correlation of LAD (p = 0.050). Multiple linear regression analysis was performed in male patients and revealed that HDL-C (β = 0.191, p = 0.002), heart rate (β = 0.182, p = 0.004), SBP (β = 0.167, p = 0.007), LVMI (β = 0.132, p = 0.032), and LAD (β = 0.165, p = 0.009) were independently associated with increasing FFA levels.ConclusionsIn patients with HCM, LVMI, LAD, HDL-C, SBP, and heart rate were independently associated with increasing plasma FFA levels in males, whereas not in females. These results suggest that sex may affect the pathogenesis of HCM through influencing FFA metabolism. And these sex-related differences should be taken into account in therapeutic approaches to influence myocardial FFA metabolism in HCM.

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The importance of having two X chromosomes

Cited by 99 publications

References 105 publications

Genetic Basis for Sex Differences in Obesity and Lipid Metabolism

Genetic Basis for Sex Differences in Obesity and Lipid Metabolism

Multifaceted origins of sex differences in the brain

Sex-related differences in the associations between plasma free fatty acid levels and clinical features in patients with hypertrophic cardiomyopathy

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