Identifying non-genetic factors associated with trigger finger.

BACKGROUND: The non-genetic factors predisposing to trigger finger (TF) have mostly been characterised in small studies from individual institutions. Here, we aimed to provide a more complete picture of TF and its associations. METHODOLOGY: This case-control study used cross-sectional data from the UK Biobank population-based cohort to identify and determine the strength of associations of phenotypic variables with TF. We performed multivariable logistic regression of a multitude of phenotypic factors associated with TF. RESULTS: We identified 2250 individuals with medical and surgical diagnostic codes for TF, and 398,495 controls. TF was found to be significantly associated with age (OR 1.04, 95% CI 1.03-1.04, P < 2.23×10-308), female sex (OR 1.22, 95% CI 1.08-1.39, P = 2.35×10-3), body mass index (OR 1.10, 95% CI 1.04-1.16, P = 5.52×10-4), carpal tunnel syndrome (OR 9.59, 95% CI 8.68-10.59, P < 2.23×10-308), Dupuytren's disease (OR 4.89, 95% CI 4.06-5.89, P < 2.23×10-308), diabetes mellitus without complications (OR 1.35, 95% CI 1.15-1.58, P = 2.03×10-4) and with complications (OR 2.46, 95% CI 1.90-3.17, P = 4.98×10-12), HbA1c (OR 1.01, 95% CI 1.01-1.02, P = 8.99×10-9), hypothyroidism (OR 1.24, 95% CI 1.07-1.43, P = 4.75×10-3) and rheumatoid arthritis (OR 1.33, 95% CI 1.06-1.68, P = 0.014). CONCLUSION: Our results provide evidence supporting the well-known risk factors such as diabetes mellitus, carpal tunnel syndrome, age and female sex. Furthermore, we can confirm putative associations such as hypothyroidism, obesity and rheumatoid arthritis, while providing evidence against others such as hypertension and hyperlipidaemia. A novel finding arising from this study is the strong association with Dupuytren's disease. Our study design allowed us to identify these associations as being independent from carpal tunnel syndrome, thereby indicating a shared pathophysiology between this disease and TF.

Health-related factors and dysregulation of epigenetic related genes in metabolic syndrome trigger finger patients and smoker trigger finger patients: preliminary analysis of patient-derived sample.

PURPOSE: To investigate the health-related factors and analyze the expression of epigenetic related genes and inflammatory genes in metabolic syndrome Trigger Finger (TF) and smoker TF. METHODS: Samples from patients' fingers with symptomatic TF were collected. There were seven groups: healthy control group, carpal tunnel syndrome (as a control for gene expression analysis), TF, diabetic TF, hypertensive TF, dyslipidemic TF and smoker TF. The expression levels of epigenetic related genes and inflammatory genes in metabolic syndrome TF and smoker TF were evaluated by the reverse transcription-polymerase chain reaction (RT-PCR) technique. The Perceived Stress Scale (PSS), Pittsburgh Sleep Quality Index (PSQI) questionnaires, disability of the arm, shoulder and hand (DASH) and numeric pain rating scale were given to the participants to fill out. RESULTS: There was a significant increase in hand dysfunction in the metabolic TF groups and smoker group compared to the TF group (p < 0.0001). The stress levels of the smoker TF group and TF with hypertension group were significantly increased compared with those in the TF group (p < 0.03) and (p < 0.021), respectively. On the other hand, there was a significant increase in the COL-I, COL-II and TNF-α gene expression of the metabolic TF groups and smoker group (p < 0.0001). CONCLUSIONS: Health-related factors in the TF tendons was highly associated with the level of inflammation and genetic alteration in TF metabolic syndromes and smoker TF patients. Therefore, further investigation is required to examine the combination of occupational therapy, gene expression, and health-related factors as a promising method of managing TF.

Genetic Risk of Trigger Finger: Results of a Genomewide Association Study.

BACKGROUND: Trigger finger, or stenosing tenosynovitis, is one of the most common conditions affecting the hand, yet its pathophysiology remains poorly understood, and genetic association studies of trigger finger are lacking. The purpose of this study was to identify single-nucleotide polymorphisms associated with trigger finger through a genomewide approach. METHODS: The authors performed a case-control genomewide association study in the Partners HealthCare Biobank. Single-nucleotide polymorphism- and gene-based association analyses were carried out after quality control, imputation, and filtering. RESULTS: Among 942 trigger finger cases and 24,472 controls, the authors tested 7,846,471 single-nucleotide polymorphisms for association with trigger finger. In the single-nucleotide polymorphism-based analysis, a single locus on chromosome 13 corresponding to KLHL1 met the genomewide significance threshold (lead single-nucleotide polymorphism rs59988404; OR, 1.74; 95 percent CI, 1.47 to 2.07; p = 1.99 × 10). After mapping, gene-based analysis demonstrated a significant association with POLE2 (p = 7.53 × 10) on chromosome 14. Among trigger finger cases, rs59988404 genotype was significantly associated with the total number of trigger finger procedures performed (p = 0.026). CONCLUSIONS: In the first reported genomewide association study of trigger finger, the authors report significant associations of KLHL1 and POLE2 with risk of trigger finger. The authors' results may help to elucidate the pathophysiology of trigger finger and facilitate an individualized, precision-medicine treatment approach. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Dysregulation of epigenetic related genes in Diabetic Trigger finger Patients; preliminary analysis of Patient-Derived Samples.

BACKGROUND: Trigger finger (TF), a painful condition involving a finger flexor tendon, is a common problem with a prevalence of ~2-3% in the general population. However, the TF prevalence is higher among diabetic patients-ranges from 6.7% to 10%. We have analyzed the expression of the extracellular matrix, inflammation, and epigenetic related genes in diabetic and non-diabetes TF. We hypothesized that Diabetes condition induces alter the expression of epigenetic modification genes in diabetic patients and one of the underlying determinants for more prevalence of TF in diabetic patients. METHOD: Tissues from the fingers of patients with symptomatic trigger fingers were collected. We had three groups: carpal tunnel syndrome (as a control), trigger finger, and diabetic trigger finger. A quantitative real-time polymerase chain reaction was performed. The gene expression of Extracellular matrix (ECM) components [COL-I, COL-II, COL-X, Aggrecan], DNA methyltransferases enzymes (DNMT1, DNMT3), growth factors (TGF-b, IGF), and Histone deacetylase enzymes (HDAC1, HDAC2) were evaluated in all groups. RESULTS: The mRNA expression of COL-I, COL-II, Aggrecan was significantly higher in the pully A1 of diabetic patients (p= 0.0164, p=0.0351, p=0.0399, respectively) as compared to non-diabetic TF patients. Diabetes was associated with a significant increase in the DNMT3 expression compared to non-diabetic TF patients (p=0.0485). HDAC1 and HDAC2 gene expression were up-regulated in diabetic TF than non-diabetic TF. CONCLUSION: The chronic state of hyperglycemia induces epigenetic modification of gene expressions in trigger fingers. This seems to have a significant impact on the development, recurrence, and progression of trigger finger in diabetic patients.

Trigger finger, tendinosis, and intratendinous gene expression.

The pathogenesis of trigger finger has generally been ascribed to primary changes in the first annular ligament. In contrast, we recently found histological changes in the tendons, similar to the findings in Achilles tendinosis or tendinopathy. We therefore hypothesized that trigger finger tendons would show differences in gene expression in comparison to normal tendons in a pattern similar to what is published for Achilles tendinosis. We performed quantitative real-time polymerase chain reaction on biopsies from finger flexor tendons, 13 trigger fingers and 13 apparently healthy control tendons, to assess the expression of 10 genes which have been described to be differently expressed in tendinosis (collagen type 1a1, collagen 3a1, MMP-2, MMP-3, ADAMTS-5, TIMP-3, aggrecan, biglycan, decorin, and versican). In trigger finger tendons, collagen types 1a1 and 3a1, aggrecan and biglycan were all up-regulated, and MMP-3and TIMP-3 were down-regulated. These changes were statistically significant and have been previously described for Achilles tendinosis. The remaining four genes were not significantly altered. The changes in gene expression support the hypothesis that trigger finger is a form of tendinosis. Because trigger finger is a common condition, often treated surgically, it could provide opportunities for clinical research on tendinosis.

A copy number variant at the KITLG locus likely confers risk for canine squamous cell carcinoma of the digit.

The domestic dog is a robust model for studying the genetics of complex disease susceptibility. The strategies used to develop and propagate modern breeds have resulted in an elevated risk for specific diseases in particular breeds. One example is that of Standard Poodles (STPOs), who have increased risk for squamous cell carcinoma of the digit (SCCD), a locally aggressive cancer that causes lytic bone lesions, sometimes with multiple toe recurrence. However, only STPOs of dark coat color are at high risk; light colored STPOs are almost entirely unaffected, suggesting that interactions between multiple pathways are necessary for oncogenesis. We performed a genome-wide association study (GWAS) on STPOs, comparing 31 SCCD cases to 34 unrelated black STPO controls. The peak SNP on canine chromosome 15 was statistically significant at the genome-wide level (P(raw) = 1.60 × 10(-7); P(genome) = 0.0066). Additional mapping resolved the region to the KIT Ligand (KITLG) locus. Comparison of STPO cases to other at-risk breeds narrowed the locus to a 144.9-Kb region. Haplotype mapping among 84 STPO cases identified a minimal region of 28.3 Kb. A copy number variant (CNV) containing predicted enhancer elements was found to be strongly associated with SCCD in STPOs (P = 1.72 × 10(-8)). Light colored STPOs carry the CNV risk alleles at the same frequency as black STPOs, but are not susceptible to SCCD. A GWAS comparing 24 black and 24 light colored STPOs highlighted only the MC1R locus as significantly different between the two datasets, suggesting that a compensatory mutation within the MC1R locus likely protects light colored STPOs from disease. Our findings highlight a role for KITLG in SCCD susceptibility, as well as demonstrate that interactions between the KITLG and MC1R loci are potentially required for SCCD oncogenesis. These findings highlight how studies of breed-limited diseases are useful for disentangling multigene disorders.

Trigger finger as an initial manifestation of familial amyloid polyneuropathy in a patient with Ile107Val TTR.

We describe a Japanese family with transthyretin Val107-related familial amyloid polyneuropathy (FAP). The clinical features were high-aged onset, sensorimotor polyneuropathy, carpal tunnel syndrome (CTS) and trigger finger. In addition, the proband showed cardiac conduction block and amyloid deposition in the sural nerve and dermis. Trigger finger may be a so far unknown clinical manifestation of Val107 FAP due to amyloid deposition in the connective tissue like CTS.