Genotype-Phenotype Relationships in Inheritable Idiopathic Pulmonary Fibrosis: A Greek National Cohort Study
Fecha
2022Language
en
Materia
Resumen
Background: Monogenic and polygenic inheritances are evidenced for idiopathic pulmonary fibrosis (IPF). Pathogenic variations in surfactant protein-related genes, telomere-related genes (TRGs), and a single-nucleotide polymorphism in the promoter of MUC5B gene encoding mucin 5B (rs35705950 T risk allele) are reported. This French-Greek collaborative study, Gen-Phen-Re-GreekS in inheritable IPF (iIPF), aimed to investigate genetic components and patients' characteristics in the Greek national IPF cohort with suspected heritability. Patients and Methods: 150 patients with familial PF, personal-family extrapulmonary disease suggesting short telomere syndrome, and/or young age IPF were analyzed. Results: MUC5B rs35705950 T risk allele was detected in 103 patients (90 heterozygous, 13 homozygous, allelic frequency of 39%), monoallelic TRG pathogenic variations in 19 patients (8 TERT, 5 TERC, 2 RTEL1, 2 PARN, 1 NOP10, and 1 NHP2), and biallelic ABCA3 pathogenic variations in 3. Overlapping MUC5B rs35705950 T risk allele and TRG pathogenic variations were shown in 11 patients (5 TERT, 3 TERC, 1 PARN, 1 NOP10, and 1 NHP2), MUC5B rs35705950 T risk allele, and biallelic ABCA3 pathogenic variations in 2. In 38 patients, neither MUC5B rs35705950 T risk allele nor TRG pathogenic variations were detectable. Kaplan-Meier curves showed differences in time-to-death (p = 0.025) where patients with MUC5B rs35705950 T risk allele alone or in combination with TRG pathogenic variations presented better prognosis. Conclusion: The Gen-Phen-Re-GreekS in iIPF identified multiple and overlapping genetic components including the rarest, underlying disease's genetic "richesse,"complexity and heterogeneity. Time-to-death differences may relate to diverse IPF pathogenetic mechanisms implicating "personalized"medical care driven by genotypes in the near future. © 2022 S. Karger AG. All rights reserved.
Colecciones
Ítems relacionados
Mostrando ítems relacionados por Título, autor o materia.
-
Evaluation of the interaction between LRRK2 and PARK16 loci in determining risk of Parkinson's disease: analysis of a large multicenter study
Wang L., Heckman M.G., Aasly J.O., Annesi G., Bozi M., Chung S.J., Clarke C., Crosiers D., Eckstein G., Garraux G., Hadjigeorgiou G.M., Hattori N., Jeon B., Kim Y.J., Kubo M., Lesage S., Lin J.J., Lynch T., Lichtner P., Mellick G.D., Mok V., Morrison K.E., Quattrone A., Satake W., Silburn P.A., Stefanis L., Stockton J.D., Tan E.K., Toda T., Brice A., Van Broeckhoven C., Uitti R.J., Wirdefeldt K., Wszolek Z., Xiromerisiou G., Maraganore D.M., Gasser T., Krüger R., Farrer M.J., Ross O.A., Sharma M. (2017)A recent study MacLeod et al. has shown that an interaction between variants at the LRRK2 and PARK16 loci influences risk of development of Parkinson's disease (PD). Our study examines the proposed interaction between LRRK2 ... -
Genetic variation in Wnt/β-catenin and ER signalling pathways in female and male elite dancers and its associations with low bone mineral density: a cross-section and longitudinal study
Amorim T., Durães C., Machado J.C., Metsios G.S., Wyon M., Maia J., Flouris A.D., Marques F., Nogueira L., Adubeiro N., Koutedakis Y. (2018)Summary: The association of genetic polymorphisms with low bone mineral density in elite athletes have not been considered previously. The present study found that bone mass phenotypes in elite and pre-elite dancers are ... -
The -938C>A polymorphism in MYD88 is associated with susceptibility to tuberculosis: A pilot study
Aggelou K., Siapati E.K., Gerogianni I., Daniil Z., Gourgoulianis K., Ntanos I., Simantirakis E., Zintzaras E., Mollaki V., Vassilopoulos G. (2016)Introduction. Tuberculosis (TB) is a major disease worldwide, caused by Mycobacterium tuberculosis (MTB) infection.The Toll- Like Receptor (TLR) pathway plays a crucial role in the recognition of MTB. Aim. The present study ...