Telomeres Length Variations in a Rheumatoid Arthritis Patients Cohort at Early Disease Onset and after Follow-Up.

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovial joint inflammation, progressive disability, premature immune aging, and telomere length (TL) shortening. Objectives: The objective of the study was to study TL changes in patients at early disease onset and after follow-up. Methods: Relative leukocyte TL (rLTL) was measured by quantitative polymerase chain reaction (qPCR) in 88 at-admission patients (AAP) with < 1 year of symptoms onset, self-compared after follow-up, and a reference group of sex- and age-matched healthy individuals. Correlations between rLTL percentage change after variable disease exposure time (DET) and clinical laboratory disease activity markers and treatments were assessed. Non-parametrical statistics were applied, considering < 0.05 p-value significant. Results: The median (p25, p75) rLTL was lower in patients after DET (0.61, 0.49-0.70) than in AAP (0.64, 0.50-0.77), p = 0.017. Furthermore, telomeres at early stages of RA were shorter than in the reference group (0.77, 0.59-0.92; p = 0.003). HLA-DRB1*04 allele carrier status did not significantly affect rLTL at an early stage and after follow-up. The patients' rLTL shortening was mainly associated with longer at-admission telomeres (OR 16.2, 95%CI: 3.5-74.4; p < 0.0001). Conclusions: At follow-up, RA patients showed significantly shorter rLTL than AAP, particularly in those AAP with longer telomeres, disregarding disease activity and treatments, denoting an rLTL shortening effect influenced by age, DET, and native rLTL.

Telomeres Length Variations in a Rheumatoid Arthritis Patients Cohort at Early Disease Onset and after Follow-Up

ABSTRACT Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovial joint inflammation, progressive disability, premature immune aging, and telomere length (TL) shortening. Objective: The objective of the study was to study TL changes in patients at early disease onset and after follow-up. Methods: Relative leukocyte TL (rLTL) was measured by quantitative polymerase chain reaction (qPCR) in 88 at-admission patients (AAP) with < 1 year of symptoms onset, self-compared after follow-up, and a reference group of sex- and age-matched healthy individuals. Correlations between rLTL percentage change after variable disease exposure time (DET) and clinical laboratory disease activity markers and treatments were assessed. Non-parametrical statistics were applied, considering < 0.05 p-value significant. Results: The median (p25, p75) rLTL was lower in patients after DET (0.61, 0.49-0.70) than in AAP (0.64, 0.50-0.77), p = 0.017. Furthermore, telomeres at early stages of RA were shorter than in the reference group (0.77, 0.59-0.92; p = 0.003). HLA-DRB1*04 allele carrier status did not significantly affect rLTL at an early stage and after follow-up. The patients' rLTL shortening was mainly associated with longer at-admission telomeres (OR 16.2, 95%CI: 3.5-74.4; p < 0.0001). Conclusion: At follow-up, RA patients showed significantly shorter rLTL than AAP, particularly in those AAP with longer telomeres, disregarding disease activity and treatments, denoting an rLTL shortening effect influenced by age, DET, and native rLTL.

Myelomeningocele genotype-phenotype correlation findings in cilia, HH, PCP, and WNT signaling pathways.

BACKGROUND: Myelomeningocele (MMC) is the most severe and frequent type of spina bifida. Its etiology remains poorly understood. The Hedgehog (Hh), Wnt, and planar cell polarity (PCP) signaling pathways are essential for normal tube closure, needing a structural-functional cilium for its adequate function. The present study aimed to investigate the impact of different gene variants (GV) from those pathways on MMC genotype-subphenotype correlations. METHODS: The study comprised 500 MMC trios and 500 controls, from 16 Telethon centers of 16 Mexican states. Thirty-four GVs of 29 genes from cilia, Hh, PCP, and Wnt pathways, were analyzed, by an Illumina on design microarray. The total sample (T-MMC) was stratified in High-MMC (H-MMC) when thoracic and Low-MMC (L-MMC) when lumbar-sacral vertebrae affected. STATA/SE-12.1 and PLINK software were used for allelic association, TDT, and gene-gene interaction (GGI) analyses, considering p value <.01 as statistically significant differences (SSD). RESULTS: Association analysis showed SSD for COBL-rs10230120, DVL2-rs2074216, PLCB4-rs6077510 GVs in T-MMC and L-MMC, and VANGL2-rs120886448 in T-MMC and H-MMC, and INVS-rs7024375 exclusively in L-MMC. TDT assay showed SSD preferential transmissions of C2CD3-rs826058 in H-MMC, and LRP5-rs3736228, and BBS2-rs1373 in L-MMC. Statistically significant GGI was observed in four in T-MMC, four completely different in L-MMC, and one in H-MMC. Interestingly, no one repeated in subphenotypes. CONCLUSIONS: Our results support an association of GVs in Hh, Wnt, PCP, and cilia pathways, with MMC occurrence location, although further validation is needed. Furthermore, present results show a distinctive panel of gene-variants in H-MMC and LMMC subphenotypes, suggesting a feasible genotype-phenotype correlation.