Role of telomere shortening in anticipation of inflammatory bowel disease

Abstract

BACKGROUND The existence of genetic anticipation has been long disputed in inflammatory bowel disease (IBD) in the absence of the explanatory mechanism. AIM To determine whether it was predictive of genetic anticipation, we evaluated telomere length in IBD. We hypothesized that multiplex IBD families exhibit a genetic defect impacting telomere maintenance mechanisms. METHODS We studied three IBD families with multiple affected members in three successive generations. We determined telomere length (TL) in lymphocytes and granulocytes from peripheral blood of the affected members using flow cytometry and fluorescence in-situ hybridization (flow FISH). We also performed whole exome sequencing in the blood of all available family members and used PhenoDB to identify potential candidate gene variants with recessive or dominant modes of inheritance. RESULTS Out of twenty-four patients of European descent selected to participate in the study, eleven patients, eight parent-child pairs affected by IBD, were included in the genetic anticipation analysis. Median difference in age at diagnosis between two successive generations was 16.5 years, with earlier age at onset in the younger generations. In most of the affected members, the disease harbored similar gastrointestinal and extraintestinal involvement but was more aggressive among the younger generations. TL was not associated with earlier age at onset or more severe disease in members of successive generations affected by IBD. NOD2 gene mutations were present in the Crohn’s disease patients of one family. However, no gene variants were identified as potential candidates for inheritance. CONCLUSION Telomere shortening appears unlikely to be involved in mechanisms of possible genetic anticipation in IBD. Further studies using a larger sample size are required to confirm or refute our findings.

Immunoepigenetic Regulation of Inflammatory Bowel Disease: Current Insights into Novel Epigenetic Modulations of the Systemic Immune Response

“…Classically, telomere shortening has been linked with dysplasia and neoplasia in ulcerative colitis [ 74 , 75 ]. A study by Truta B et al found no clear link between telomere shortening in anticipation of IBD, although the authors stated that more studies are needed with larger sample sizes to confirm or refute their findings [ 75 ].…”

“…Classically, telomere shortening has been linked with dysplasia and neoplasia in ulcerative colitis [ 74 , 75 ]. A study by Truta B et al found no clear link between telomere shortening in anticipation of IBD, although the authors stated that more studies are needed with larger sample sizes to confirm or refute their findings [ 75 ]. Nevertheless, age-related telomere loss could contribute to immune dysfunction and the autoimmune response and could therefore explain the onset of IBD after middle age.…”

Telomere dysfunction in some pediatric congenital and growth-related diseases

“…Similarly, Isaevska et al ( 104 ) reported that for pregnant mothers, air pollution factors were related to shorter telomeres at birth, which can increase the long-term incidence of asthma and other diseases in children. In the study of Chakravarti et al ( 46 ) found that telomere dysfunction leads to activation of ATM/YAP1 pathway, which is related to the pathogenesis and severity of inflammatory bowel disease (IBD).However, some scholars also believe that no evidence has been found that TL is associated with IBD in children ( 47 , 48 ).…”

Telomere pathology in ontogenesis in patients with Turner syndrome

“…В связи с тенденцией к персонализации медицины и поиску геномных, протеомных и метаболомных предикторов внутренних болезней активно изучается корреляция длины теломер у пациентов с соматической патологией: нарушениями углеводного обмена [ 9 ][ 10 ], сердечно-сосудистыми заболеваниями [ 11 ], воспалительными заболеваниями желудочно-кишечного тракта [ 12 ], ожирением [13–15] и т.д.…”