Nonrandom chromosome changes in multiple sclerosis

D'Alessandro, E.; Cola, Mario Di; Re, Maria Luisa Lo; Ligas, Claudio; Vaccarella, Corinna; D’Andrea, Francesco; Marini, Carmine; Prencipe, Massimiliano

doi:10.1002/ajmg.1320370322

Cited by 10 publications

(8 citation statements)

References 28 publications

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“…However, our study was designed to assess global rather than locus-specific genetic contributions to disease, thus we were able to identify significant chromosome-wide heterogeneity across sexes and male association enrichment for CAD on the X chromosome. Likewise, MS has been suggested to have X-linked risk via mouse models and association with X aneuploidy (D'Alessandro et al 1990;Smith-Bouvier et al 2008;Seminog et al 2015), but, to our knowledge, not genome-wide studies before ours (Chang et al 2014). Additionally, a recent study (Chang et al 2014) hypothesized sexually dimorphic effect sizes for X-linked genes in autoimmune diseases.…”

Section: Discussionmentioning

confidence: 98%

Genetic Mechanisms Leading to Sex Differences Across Common Diseases and Anthropometric Traits

et al. 2017

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Common diseases often show sex differences in prevalence, onset, symptomology, treatment, or prognosis. Although studies have been performed to evaluate sex differences at specific SNP associations, this work aims to comprehensively survey a number of complex heritable diseases and anthropometric traits. Potential genetically encoded sex differences we investigated include differential genetic liability thresholds or distributions, gene-sex interaction at autosomal loci, major contribution of the X-chromosome, or gene-environment interactions reflected in genes responsive to androgens or estrogens. Finally, we tested the overlap between sex-differential association with anthropometric traits and disease risk. We utilized complementary approaches of assessing GWAS association enrichment and SNP-based heritability estimation to explore explicit sex differences, as well as enrichment in sex-implicated functional categories. We do not find consistent increased genetic load in the lower-prevalence sex, or a disproportionate role for the X-chromosome in disease risk, despite sex-heterogeneity on the X for several traits. We find that all anthropometric traits show less than complete correlation between the genetic contribution to males and females, and find a convincing example of autosome-wide genome-sex interaction in multiple sclerosis (P = 1 × 10). We also find some evidence for hormone-responsive gene enrichment, and striking evidence of the contribution of sex-differential anthropometric associations to common disease risk, implying that general mechanisms of sexual dimorphism determining secondary sex characteristics have shared effects on disease risk.

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Section: Discussionmentioning

confidence: 98%

Genetic Mechanisms Leading to Sex Differences Across Common Diseases and Anthropometric Traits

et al. 2017

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“…Another study involving the X chromosome, a cytogenetic analysis in patients with MS, identified abnormal X chromosomes in 50% of the study cohort. Abnormalities were premature centromere division and structural aberrations that could imply a preferential clustering of chromosomal breakpoints (139). Correlation between clinical and cytogenetic data also showed that cytogenetic abnormalities were prevalent in patients with a high relapse frequency or with progressive forms of the disease (139).…”

Section: The X Chromosomementioning

confidence: 90%

SeXX Matters in Multiple Sclerosis

2020

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Multiple sclerosis (MS) is the most common chronic inflammatory and neurodegenerative disease of the central nervous system (CNS). An interesting feature that this debilitating disease shares with many other inflammatory disorders is that susceptibility is higher in females than in males, with the risk of MS being three times higher in women compared to men. Nonetheless, while men have a decreased risk of developing MS, many studies suggest that males have a worse clinical outcome. MS exhibits an apparent sexual dimorphism in both the immune response and the pathophysiology of the CNS damage, ultimately affecting disease susceptibility and progression differently. Overall, women are predisposed to higher rates of inflammatory relapses than men, but men are more likely to manifest signs of disease progression and worse CNS damage. The observed sexual dimorphism in MS may be due to sex hormones and sex chromosomes, acting in parallel or combination. In this review, we outline current knowledge on the sexual dimorphism in MS and discuss the interplay of sex chromosomes, sex hormones, and the immune system in driving MS disease susceptibility and progression.

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“…It can be concluded that the tested combination did not manifest significant clastogenic effects, nor that it showed particular protective potentials. Furthermore the treatment with the test combination did not record serious chromosome aberrations such as the ring chromosomes, acentric fragments, 10 and dicentric chromosomes. An increase in numeric aberrations and aneuploidy was recorded after the treatment with the test substances.…”

Section: Resultsmentioning

confidence: 91%

“…Patients with immune-mediated disease, including the MS patients, had aberrant lymphocyte clones that were stimulated by auto-antigens (9)(10)(11). A hypothesis regarding patients with auto-immune disease proposed that the treatment with certain active substances may normalize cytogenetic lymphocyte abnormalities what could suggest substances potential for therapeutic treatment.…”

Section: Introductionmentioning

confidence: 99%

Cytogenetic effects of combination of tridecactide and met-enkephalin on lymphocytes of patients with multiple sclerosis

Rakanović-Todić

Ibrulj

Burnazović-Ristić

et al. 2015

JHSCI

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Introduction:The met-enkephalin (1-5 Adrenorphin) and tridecactide (alpha-corticotropin 1-13) combination is used in the multiple sclerosis (MS) immuno-modulatory treatment. A testing of cytogenetic effects of met-enkephalin resulted in reductions of lymphocytic aberrations in the in the lymphocytes of the peripheral blood (PBL) of patients with immune-mediated diseases. The aim of this research is to evaluate the in vitro effects of the combination of the met-enkephalin and tridecactide on the number and the type of chromosome aberrations in PBL of the MS patients. Methods:We used blood samples from seven female patients with the diagnosis multiple sclerosis based on a McDonald Diagnostic Criteria. The tested combination, met-enkephalin and alpha-ACTH 1-13 was added at three different concentrations and constant volume. Results:Results showed that the combination of tested substances did not reduce the number of structural aberrations, although the treatment did not result in severe aberrations such as ring, fragmented, and dicentric chromosomes. Furthermore, it elicited an increase in the number of numerical aberrations and aneuploidy after the treatment with the test combo. Conclusion:As the changes in ploidy significantly change the DNA as well as the biochemical cell phenotype, we concluded that more research in this field should be conducted, including both toxicological as well as the pharmacodynamic considerations.

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Nonrandom chromosome changes in multiple sclerosis

Cited by 10 publications

References 28 publications

Genetic Mechanisms Leading to Sex Differences Across Common Diseases and Anthropometric Traits

Genetic Mechanisms Leading to Sex Differences Across Common Diseases and Anthropometric Traits

SeXX Matters in Multiple Sclerosis

Cytogenetic effects of combination of tridecactide and met-enkephalin on lymphocytes of patients with multiple sclerosis

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