Effects of antiviral drug therapy on dynamic thiol/disulphide homeostasis and nitric oxide levels in COVID-19 patients.

The novel coronavirus disease 2019 (COVID-19) has led to a serious global pandemic. Although an oxidative stress imbalance occurs in COVID-19 patients, the contributions of thiol/disulphide homeostasis and nitric oxide (NO) generation to the pathogenesis of COVID-19 have been poorly identified. Therefore, the aim of this study was to evaluate the effects of antiviral drug therapy on the serum dynamics of thiol/disulphide homeostasis and NO levels in COVID-19 patients. A total of 50 adult patients with COVID-19 and 43 sex-matched healthy control subjects were enrolled in this prospective study. Venous blood samples were collected immediately on admission to the hospital within 24 h after the diagnosis (pre-treatment) and at the 15th day of drug therapy (post-treatment). Serum native thiol and total thiol levels were measured, and the amounts of dynamic disulphide bonds and related ratios were calculated. The average pre-treatment total and native thiol levels were significantly lower than the post-treatment values (P < 0.001 for all). We observed no significant changes in disulphide levels or disulphide/total thiol, disulphide/native thiol, or native thiol/total thiol ratios between pre- and post-treatments. There was also a significant increase in serum NO levels in the pre-treatment values when compared to control (P < 0.001) and post-treatment measurements (P < 0.01). Our results strongly suggest that thiol/disulphide homeostasis and nitrosative stress can contribute to the pathogenesis of COVID-19. This study was the first to show that antiviral drug therapy can prevent the depletion in serum thiol levels and decrease serum NO levels in COVID-19 patients.

Comparison of serum dynamic thiol/disulphide homeostasis and nitric oxide levels of total intravenous vs inhaled anaesthesia in endoscopic transsphenoidal pituitary surgery.

BACKGROUND: Transsphenoidal pituitary surgery (TPS) is traditionally performed under general anaesthesia. This study aimed to compare the effects of total intravenous anaesthesia (TIVA) or sevoflurane, an inhalation anaesthetic, on thiol-disulphide homeostasis in patients undergoing endoscopic endonasal TPS. METHODS: In this study, 84 patients scheduled for TPS were randomly categorised into two groups: propofol (n = 42, the TIVA group) or sevoflurane (n = 42, the SEVO group). Blood samples were taken before induction of general anaesthesia and at the 30 minutes of postoperation. Serum native thiol and total thiol levels were detected, and the number of dynamic disulphide bonds and related ratios were calculated from these values. Serum nitric oxide (NO) levels were measured using a chemiluminescence method. RESULTS: Although native thiol levels in TIVA postoperation group were markedly increased (P < .05), total thiol levels in SEVO postoperation group were significantly decreased (P < .01). Disulphide levels were declined in both groups (P < .05 for TIVA and P = .001 for SEVO groups). Disulphide/native thiol (P < .05 for both groups) and disulphide/total thiol ratios (P < .05 for TIVA and P < .01 for SEVO groups) were depressed in postoperation groups. We found a marked elevation in native thiol/total thiol ratio in both groups (P < .05 for TIVA and P < .01 for SEVO groups). There was significant augmentation in serum NO levels in the SEVO postoperation group (P < .05). CONCLUSION: These results are the first to show that both TIVA and sevoflurane showed similar antioxidant effect with reduced disulphide levels, but sevoflurane may offer more robust oxidative stress protection and augmented NO production than TIVA during TPS. However, the clinical effect is needed to further investigate.

Effectiveness Oral Theophylline, Piracetam, and Iron Treatments in Children With Simple Breath-Holding Spells.

Breath-holding spells (BHS) are common nonepileptic paroxysmal events in children. This is a retrospective study to compare the effectiveness of oral theophylline, piracetam, and iron treatments in children with simple BHS. A total of 146 children (75 girls and 71 boys) with simple BHS were included to this retrospective study. Children were divided into 4 groups: nontreated (no anemia and no treatment), oral theophylline (10 mg/kg/d as a single daily dose), piracetam (40 mg/kg/d in 2 divided doses), and elementary iron (3 mg/kg/d as a single daily dose) treatments. Iron therapy had been given only in children with iron deficiency anemia. Neurologic, cardiologic, and biochemical evaluations were performed for all children. The majority of the patients had cyanotic spells (83.6%). The frequency of attacks/month was markedly decreased with iron (58.8%) and theophylline (82.9%) treatments, but not with piracetam therapy (8.8%) and nontreated group (4.7%). Satisfaction of the parents/caregivers was found to be high in the theophylline group (P < .001). Our results showed that theophylline was the most effective therapy to decrease the frequency of simple BHS in children.

Investigation of leukocyte RHO/ROCK gene expressions in patients with non-valvular atrial fibrillation.

Atrial fibrillation (AF) is an arrhythmia caused by disorganized electrical activity in the atria, and it is an important cause of mortality and morbidity. There is a limited data about Rho/Rho-kinase (ROCK) pathway contribute to AF development. The aim of the present study was to elucidate leukocyte RHO/ROCK gene expressions in patients with non-valvular AF (NVAF). A total of 37 NVAF patients and 47 age and sex-matched controls were included in this study. mRNA was extracted from leukocytes, and real-time polymerase chain reaction was used for gene expression analysis. A marked increase in ROCK1 and ROCK2 gene expressions in patients with NVAF was observed (P<0.0001). The present study detected significant elevations in RHOBTB2, RND3 (RHOE), RHOC, RHOG, RHOH, RAC3, RHOB, RHOD, RHOV, RHOBTB1, RND2, RND1 and RHOJ gene expressions (P<0.01). However, there were marked decreases in CDC42, RAC2, and RHOQ gene expressions in patients with NVAF. No significant modifications were seen in the other Rho GTPase proteins RHOA, RAC1, RHOF, RHOU and RHOBTB3. To the best of our knowledge, the present study is the first to provide data that gene expression of leukocyte RHO/ROCK may contribute to the NVAF pathogenesis through activated leukocytes, which promotes the immune or inflammatory cascade.

Determination of dynamic thiol/disulphide homeostasis in children with tetralogy of Fallot and ventricular septal defect.

Oxidative stress may contribute to the pathogenesis of congenital heart defects, but the role of dynamic thiol/disulphide homeostasis has not been evaluated. The objective of this study was to assess whether there are changes in thiol/disulphide homeostasis and nitric oxide levels in children with tetralogy of Fallot (TOF) and ventricular septal defect (VSD). A total of 47 children with congenital heart defects (24 TOF and 23 VSD) and 47 healthy age- and sex-matched controls were included in this study. Serum total thiol and native thiol levels were measured using a novel automatic spectrophotometric method. The amount of dynamic disulphide bonds and related ratios were calculated from these values. Serum nitric oxide levels were detected using a chemiluminescence assay. We found that the average native thiol, total thiol, and disulphide levels were decreased in patients with VSD when compared with healthy individuals (p < 0.001, p < 0.001, and p < 0.01, respectively). While native thiol levels were decreased (p < 0.01), disulphide levels were elevated in the TOF group (p < 0.05). We observed marked augmentation of disulphide/native thiol (p < 0.001) and disulphide/total thiol ratios (p < 0.01) in the TOF group. However, there was a significant decrease in native thiol/total thiol ratio in patients with TOF. No significant changes in these ratios were noted in the VSD group. We detected significant elevations in serum nitric oxide levels in children with TOF and VSD (p < 0.001 for all). These results are the first to demonstrate that thiol/disulphide homeostasis and nitric oxide are associated with TOF and VSD in children.

Investigation of Dynamic Thiol/Disulfide Homeostasis in Children With Acute Immune Thrombocytopenia.

Oxidative stress may play a role in the pathogenesis of immune thrombocytopenia (ITP), but the role of dynamic thiol/disulfide homeostasis has not been studied. The objective of this study was to assess whether there is a change in thiol/disulfide homeostasis in children with acute ITP. A total of 40 children with acute ITP and 50 healthy age-matched and sex-matched controls were included in this study. Serum total thiol and native thiol levels have been measured with a novel automatic spectrophotometric method. The amount of dynamic disulfide bonds and related ratios were calculated from these values. The average total thiol and native thiol levels of the patient group were found to be significantly lower than those levels of controls (P<0.01). However, intravenous immunoglobulin (IVIG) treatment with 1 g/kg/d prevented these reductions. disulfide level was slightly, but not significantly, depressed in ITP patients, but it recovered following IVIG treatment. We detected no marked changes in disulfide/total thiol, disulfide/native thiol, and native thiol/total thiol ratios between groups. These results are the first to demonstrate that thiol/disulfide homeostasis plays a role in ITP pathogenesis, and IVIG treatment can prevent the reduced thiol levels in children.

Increased Expressions of ICAM-2 and ICAM-3 in Pterygium.

Purpose: Pterygium, one of the most common ocular surface diseases, is characterized by inflammatory infiltrates, proliferation, angiogenesis, fibrosis, and extracellular matrix breakdown. The objective of this study was to elucidate the levels of the intercellular adhesion molecule (ICAM)-2, and ICAM-3 gene and protein expressions in pterygium. Methods: A total of 59 patients with pterygium were included in this study. mRNA from pterygial and conjunctival autograft tissues were extracted, and real-time polymerase chain reaction on the BioMark HD dynamic array system was performed for the ICAM-2 and ICAM-3 gene expressions. ICAM-2 and ICAM-3 protein expressions using western blot and immunohistochemistry methods were also investigated in pterygial and conjunctival autograft tissues. Results: ICAM-2 and ICAM-3 gene expressions were markedly augmented in pterygial tissues (P = 0.0018 and P = 0.0023, respectively). Significant increases in protein expressions in pterygial tissues were also detected for ICAM-2 and ICAM-3 (P = 0.0116 and P = 0.0252, respectively). In the immunohistochemical studies, there was a marked increase in ICAM-3 (P = 0.0152), but not in ICAM-2 (P = 0.1041), protein expressions in pterygial tissues. Significant positive correlations between pterygia grading with ICAM-2 protein expression (P = 0.0398) and ICAM-3 immunohistochemical scores (P = 0.0138) were observed. Conclusion: These results demonstrate, for the first time, the expressions of ICAM-2 and ICAM-3 in the pterygium. These findings may help to understand the signal transduction mechanisms in the pterygium formation and provide a new therapy strategy for pterygium treatment.

Dynamic thiol/disulfide homeostasis in children with community-acquired pneumonia.

BACKGROUND: Alteration in thiol level under oxidative stress may contribute to community-acquired pneumonia (CAP). The goal of this study was to determine whether there are changes in thiol/disulfide homeostasis and nitric oxide (NO) in children with CAP. METHODS: In total, 130 participants were involved in the study. Of these, 65 had been diagnosed with CAP on admission, and the remaining 65 were healthy individuals. Serum total thiol and native thiol were measured in each participant using a novel automated spectrophotometric method. The amount of dynamic disulfide bonds and related ratios were calculated from these values. Serum NO was measured on chemiluminescence assay. RESULTS: Average native thiol, total thiol, and disulfide in the CAP group were significantly lower than in the healthy individuals (P < 0.0001, P < 0.0001, P = 0.0126, respectively). In addition, disulfide/native thiol (P = 0.0002), and disulfide/total thiol ratios (P = 0.0004) were significantly higher, whereas the native thiol/total thiol ratio (P = 0.0004) was lower in the CAP group. High serum NO was noted in the CAP group (P = 0.0003), but there was no marked correlation between thiol/disulfide and NO. CONCLUSION: The changes in endogenous thiol levels under oxidative stress may be associated with the pathogenesis of CAP in pediatric patients.

Respiratory Distress and Severe Anemia in a Child With Idiopathic Pulmonary Hemosiderosis.

Idiopathic pulmonary hemosiderosis is an infrequent cause of pulmonary hemorrhage in children. It is classically defined by the triad of recurrent hemoptysis, iron-deficiency anemia, and diffuse parenchymal infiltration without an obvious cause. The pathogenesis remains unexplained, diagnosis may be difficult, and the clinical course exceedingly variable. A 4-year-old girl was admitted to the hospital with complaints of dyspnea, and skin and mucous membrane pallor. The suspicion of idiopathic pulmonary hemosiderosis led to the use of corticosteroid therapy with rapid improvement in clinical condition and discharge from hospital.

Contribution of the Rho-kinase to Systemic Sclerosis and Behçet's Disease.

BACKGROUND: The small GTPase Rho family and its effectors, Rho-kinases (ROCK) play essential roles in the actin cytoskeleton organization and coordinate a broad range of cellular functions, such as inflammatory responses, cell contractility, migration, adhesion, proliferation, and apoptosis. METHODS: The goal of this work is to review existing literature about systemic sclerosis and Behçet's disease in relation to ROCK. RESULTS: There are some evidence that ROCK expression is elevated in patients with systemic sclerosis and Behçet's disease. Rho/ROCK gene polymorphisms have been shown to be associated with these disorders. Endothelial function is also impaired in these autoimmune diseases. Rho/Rho-kinase pathway might have a crucial role in endothelial, vascular, and fibrotic pathologies. CONCLUSION: Dysregulation in the Rho/ROCK pathway may represent a common pathogenic mechanism in multiple autoimmune disorders. Current evidence indicate that Rho/ROCK genes might be risk factors, and can contribute to susceptibility and development of systemic sclerosis and Behçet's disease. These studies may also provide important insights into the future development or use of potential novel therapeutic approaches, such as selective Rho-kinase inhibitors, for the treatment of patients with systemic sclerosis and Behçet's disease.

Association of Neutrophil/Lymphocyte Ratio With Intravenous Immunoglobulin Treatment in Children With Guillain-Barré Syndrome.

Guillain-Barré syndrome (GBS) is an acute immune-mediated inflammatory polyneuropathy of the peripheral nervous system. The authors aimed to investigate whether the neutrophil/lymphocyte (N/L) and platelet/lymphocyte (P/L) ratios are the parameters that associated with the drug treatment or severity of GBS. Twenty-seven children with GBS were retrospectively analyzed from the medical records of patients who attended to the Pediatric Neurology Department of the Gaziantep University Hospital. Biochemical and hematologic parameters were measured. Leukocytes, neutrophils counts and N/L ratio were significantly higher before the intravenous immunoglobulin treatment ( P < .001). However, there were no marked differences in platelet count and P/L ratio. In addition, marked correlation was observed between the N/L ratio after treatment and duration of weakness. The results of the study showed that N/L ratio is significantly higher in GBS patients, and reduces following with intravenous immunoglobulin treatment.

Serial Casting as an Adjunct to Botulinum Toxin Type A Treatment in Children With Cerebral Palsy and Spastic Paraparesis With Scissoring of the Lower Extremities.

The purpose of this study was to examine whether combination therapy of serial casting and botulinum toxin type A injection can further enhance the effects of botulinum toxin type A in children with cerebral palsy with scissoring of both legs. This study was a prospective and randomized trial. The children were divided into 2 groups, one of which received serial casting after botulinum toxin type A (n = 40), and the other which only received botulinum toxin type A (n = 40). Serial casting started 3 weeks after the botulinum toxin type A. Both groups received physiotherapy. Groups were assessed at baseline then compared at 6 and 12 weeks following the intervention. Significant improvements in Gross Motor Function Measure-66 and Caregiver Health Questionnaire were recorded in both groups ( P < .001). The modified Ashworth scale improved significantly following botulinum toxin type A in the serial casting group ( P < .05), but not in botulinum toxin type A only group. These results suggest that serial casting after botulinum toxin type A can enhance the benefits of botulinum toxin type A in children with cerebral palsy.

Association of Rho-kinase Gene Polymorphisms with Respiratory Distress Syndrome in Preterm Neonates.

BACKGROUND: Respiratory distress syndrome (RDS) of the newborn is one of the most common causes of morbidity and mortality in preterm infants. Our objective was to determine the association between Rho-kinase (ROCK1 and ROCK2) gene polymorphisms and RDS in preterm neonates. METHODS: A total of 193 preterm infants with RDS and 186 preterm infants without respiratory problems were included in this study. Polymorphisms were analyzed in genomic DNA using a BioMark 96.96 dynamic array system. RESULTS: We observed that ROCK1 gene rs2271255 (Lys222Glu) and rs35996865 polymorphisms, and ROCK2 gene rs726843, rs2290156, rs10178332, and rs35768389 (Asp601Val) polymorphisms were associated with RDS. However, no associations were found with rs73963110, rs1515219, rs965665, rs2230774 (Thr431Asn), rs6755196, and rs10929732 polymorphisms. Additionally, 12 haplotypes (6 in ROCK1 and 6 in ROCK2) were found to be markedly associated with RDS. CONCLUSION: This is the first study to examine the involvement of ROCK gene variation in the risk of incident RDS. The results strongly suggest that ROCK gene polymorphisms may modify individual susceptibility to RDS in the Turkish population.

Toward Novel Diagnostics for Primary Open-Angle Glaucoma? An Association Study of Polymorphic Variation in Ras Homolog Family Member (A, B, C, D) Genes RHOA, RHOB, RHOC, and RHOD.

The annual economic burden of visual disorders in the United States was estimated as $139 billion. The World Health Organization has listed glaucoma in the top 10 priority eye diseases. Primary open-angle glaucoma (POAG) is a common subtype, with a lack of clinical tools for early diagnosis. The Rho GTPases belong to the Ras superfamily of proteins; the RhoA immunostaining in the optic nerve head in human glaucoma is reportedly increased. We investigated the association of polymorphisms in the Ras Homolog Family Member A, B, C, and D genes (RHOA, RHOB, RHOC, and RHOD, respectively). In a total sample of 361 unrelated subjects (179 patients with POAG and 182 age- and sex-matched healthy controls), RHOA (rs6784820, rs974495), RHOB (rs62121967), RHOC (rs11102522), and RHOD (rs61891303, rs2282502) polymorphisms were characterized by the BioMark HD dynamic array system with real-time polymerarse chain reaction. Among these candidate genetic markers and considering the Bonferroni correction, RHOA rs974495 polymorphism was significantly associated with POAG (p = 0.0011), with the TT genotype increasing the disease risk 4.9 times (95% CI 1.630-15.023). The allele and haplotype distributions of the above RHO candidate polymorphisms did not diplay a significant association. This is the first study, to the best of our knowledge, to identify a significant genotypic association between POAG and RHOA gene rs974495 polymorphism. These observations warrant replication in independent samples in the pursuit of precision medicine for rapid and early glaucoma diagnosis, and molecular targets for innovation in therapeutics of this common eye disease.

Evidence for elevated (LIMK2 and CFL1) and suppressed (ICAM1, EZR, MAP2K2, and NOS3) gene expressions in metabolic syndrome.

The metabolic syndrome (MetS) is a common multicomponent condition including abdominal obesity, dyslipidemia, hypertension, and hyperglycaemia. The aim of this study was to investigate the associations of the expression of a panel of signalling genes with the MetS in a Turkish population. A total of 54 MetS patients and 42 healthy controls with similar age and sex were included to this study. mRNA from blood samples was extracted, and real-time polymerase chain reaction was performed for gene expressions using a BioMark 96.96 dynamic array system. We observed marked increases in LIM kinase 2 (LIMK2) and cofilin 1 (CFL1) gene expressions in MetS patients. However, there were significant decreases in intercellular adhesion molecules 1 (ICAM1), ezrin (EZR), mitogen-activated protein kinase kinase 2 (MAP2K2), and nitric oxide synthase 3 (NOS3) gene expressions in MetS patients. Additionally, no marked changes were noted in other 15 genes studied. This is the first study to provide evidence that activation of LIMK2/CFL1 pathway may play an important role in MetS.

CYP gene expressions in obesity-associated metabolic syndrome.

PURPOSE: The contribution of cytochrome P450 (CYP) gene expressions in metabolic syndrome (MetS) has not been elucidated, and was the aim of this study. METHODS: A total of 51 MetS patients and 41 healthy controls with similar age and sex were included to this study. mRNA from blood samples was extracted, and real-time polymerase chain reaction was performed for gene expressions using a dynamic array system. RESULTS: We observed marked suppressions in CYP2A6 (p=0.0123), CYP4F2 (p=0.0005), CYP3A5 (p=0.0003), and CYP17A1 (p<0.0001) gene expressions in MetS patients. CONCLUSIONS: This is the first study to provide evidence that depressed expressions of CYP2A6, CYP4F2, CYP3A5, and CYP17A1 genes may play a role in MetS.

Comparison of Efficacy and Side Effects of Oral Baclofen Versus Tizanidine Therapy with Adjuvant Botulinum Toxin Type A in Children With Cerebral Palsy and Spastic Equinus Foot Deformity.

This retrospective study aimed to compare the therapeutic response, including side effects, for oral baclofen versus oral tizanidine therapy with adjuvant botulinum toxin type A in a group of 64 pediatric patients diagnosed with static encephalopathy and spastic equinus foot deformity. Following botulinum toxin A treatment, clinical improvement led to the gradual reduction of baclofen or tizanidine dosing to one-third of the former dose. Gross Motor Functional Measure and Caregiver Health Questionnaire scores were markedly elevated post-botulinum toxin A treatment, with scores for the tizanidine (Gross Motor Functional Measure: 74.45 ± 3.72; Caregiver Health Questionnaire: 72.43 ± 4.29) group significantly higher than for the baclofen group (Gross Motor Functional Measure: 68.23 ± 2.66; Caregiver Health Questionnaire: 67.53 ± 2.67, P < .001). These findings suggest that the combined use of botulinum toxin A and a low dose of tizanidine in treating children with cerebral palsy appears to be more effective and has fewer side effects versus baclofen with adjuvant botulinum toxin A.

Investigation of the Rho-kinase Gene Polymorphism in Primary Open-angle Glaucoma.

PURPOSE: Genetic factors are shown to have a role in the development of primary open-angle glaucoma (POAG). The aim of this study was to determine the effects of genetic polymorphisms of Rho-kinase (ROCK) genes on the risk of POAG in a Turkish population. METHODS: Genomic DNA was extracted from leukocytes of the peripheral blood, and 8 single nucleotide polymorphisms in the ROCK1 and ROCK2 genes were analysed in 179 patients with POAG and in 182 healthy controls of similar age by using BioMark HD dynamic array system. RESULTS: Neither genotype distributions nor the allele frequencies for the ROCK1 (rs35996865) and ROCK2 [rs2290156, rs965665, rs10178332, rs2230774 (Thr431Asn), rs2230774 (Thr431Ser), rs6755196, and rs726843] gene polymorphisms showed a significant difference between the groups. There were also no marked associations between the haplotype frequencies and POAG. CONCLUSIONS: This is the first study to examine the involvement of ROCK1 and ROCK2 gene variations in the risk of POAG development. This study demonstrated that the polymorphisms studied are not associated with the increased risk of development of POAG in the Turkish population.

Investigation of Rho-Kinase Expressions and Polymorphisms in Mantle Cell Lymphoma Patients.

OBJECTIVE: Mantle cell lymphoma (MCL) is a rare but aggressive form of B-cell non-Hodgkin lymphoma characterized by excessive expression of cyclin D1. Intracellular signaling enzyme Rho-kinase (ROCK) can contribute to cellular migration, proliferation, and differentiation, as well as tumor development and metastasis. However, ROCK gene and protein expressions or polymorphisms have never been investigated in MCL patients. The purpose of this study was to investigate the role of ROCK gene and protein expressions in MCL patients. We also examined ROCK2 gene polymorphisms in this study. MATERIALS AND METHODS: A total of 60 patients with MCL and 60 healthy controls were included in this retrospective study. Hematoxylin and eosin-stained lymph node tissue slides in the entire archive were reevaluated and used for immunohistochemistry, gene expression, and polymerase chain reaction studies. RESULTS: In immunohistochemical studies, there were significant increases in ROCK1 (p=0.0009) and ROCK2 (p<0.0001) protein expressions in MCL patients when compared with the control group. Although a marked increase in ROCK1 gene expression (p=0.0215) was noted, no significant change was observed in ROCK2 gene expression in MCL patients. Seven ROCK2 polymorphisms were studied, but the results showed no significant differences between the groups. CONCLUSION: This is the first study to show that ROCK1 gene and ROCK protein expressions may contribute to the development of MCL.

Association of TRPM Channel Gene Polymorphisms with Systemic Sclerosis.

BACKGROUND/AIM: Systemic sclerosis (SSc) is an inflammatory disease characterized by vascular abnormalities and fibrosis. The aim of the present study was to investigate the possible role of transient receptor potential melastatin (TRPM) channel genes in the susceptibility and phenotype expression of SSc. MATERIALS AND METHODS: A total of 339 patients with SSc and 302 healthy controls were studied. Genomic DNA was extracted from leukocytes of the peripheral blood, and 25 single nucleotide polymorphisms in the TRPM channel genes were analyzed by the BioMark HD dynamic array system. RESULTS: There were marked increases in the CC genotype (94.7% vs 81.8%, p<0.0001) and C allele frequencies (97.0% vs. 90.1%, p<0.0001) in the TRPM3 rs1328142, and TT genotype (19.0% vs. 7.8%, p=0.0002) in TRPM5 rs34551253 (Ala456Thr) polymorphism in SSc patients when compared to controls. TRPM3 gene rs1328142 polymorphism was also markedly associated with disease phenotype. However, no associations with the other 23 polymorphisms studied were found. CONCLUSION: This is the first study to examine the involvement of TRPM channel gene variations on the risk of SSc incidence. Our results suggest roles of TRPM3 and TRPM5 gene variants in the susceptibility to or clinical expression of SSc in the Turkish population.