IL-17 and IL-38 gene polymorphisms in thyroid-associated ophthalmopathy.

BACKGROUND: Thyroid-associated ophthalmopathy (TAO) is an autoimmune condition commonly linked with Graves' disease (GD), characterized by orbital tissue inflammation and fibrosis. It is hypothesized that gene polymorphisms may influence production of the IL-17 and IL-38 cytokines, thereby impacting TAO development and progression. This study focused on investigating the gene polymorphisms of IL-17 (rs9463772 C/T in IL17F) and IL-38 (rs3811058 C/T, rs7570267 A/G in IL1F10) in patients with GD. METHODS: A case-control study was conducted on 132 patients with TAO and 153 patients without TAO according to eligibility criteria. After clinical examination blood samples were collected for further investigations. Genotyping was performed with the TaqMan™ Master Mix kit. Allele and genotype frequencies were compared between studied groups and subgroups. RESULTS: No significant differences were found in age, duration of GD, or thyroid hormone between patients with and without TAO. However, a higher predisposition to develop TAO was observed among smokers (OR = 1.682, p = 0.03). Overall, no significant associations between gene polymorphisms and TAO development were identified in GD patients. Further analysis revealed that the CC genotype in IL1F10 rs3811058 polymorphism among Caucasians was associated with an increased risk of TAO (OR = 2.7, p = 0.02), as well as allele differences were also significant (OR = 2.8, p = 0.001). CONCLUSIONS: These findings shed light on TAO genetic predispositions in Kazakhstani GD patients, notably among Caucasians, underscoring the need for further research. These results may offer valuable targets for the development of novel treatments for TAO.

Assessment of the levels of interleukin-17 and interleukin-38 in thyroid-associated ophthalmopathy patients.

PURPOSE: The objective of the study was to analyse the levels of IL-17 and IL-38 in the samples of unstimulated tears, orbital adipose tissues, and sera of patients diagnosed with active forms of TAO. The correlation of the levels of IL-17 and IL-38 with clinical activity score (CAS) was scrutinized. METHODS: A study was conducted at the Kazakhstan Scientific Research Institute of Eye Diseases (Almaty city, Kazakhstan). Study participants (n = 70) were sub-divided into 3 groups: (1) a group of patients diagnosed with active TAO (n = 25), (2) a group of patients with an inactive form of TAO (n = 28), and (3) a "control group" (patients diagnosed with orbital fat prolapse, n = 17). All patients underwent a clinical assessment and diagnostics. The activity of the disease and its severity were assessed using the CAS and NOSPECS scales. Thyroid function tests were performed, including the study of the levels of thyroid-stimulating hormone, triiodothyronine, free thyroxine, and antibodies to the thyroid-stimulating hormone receptor. IL-17 and IL-38 levels in non-stimulated tear samples, orbital tissue, and patients' sera were measured using commercial ELISA kits. RESULTS: The results showed that the number of former smokers prevailed among patients with active TAO (48%) in comparison with patients with inactive TAO (15.4%), p = 0.001. The concentration of IL-17 significantly increased in the samples of non-stimulated tears, adipose tissues of the orbit and sera of patients with active forms of TAO. The level of IL-38 was reduced in all types of samples (p ≤ 0.05). The results of a histological study of orbital adipose tissues in the group of patients with an active form of TAO showed the presence of focal infiltration with lymphocytes, histiocytes, plasma cells, severe sclerosis and vascular plethora. We observed an association between the CAS of patients with active TAO and the level of IL-17 in sera (r = 0.885; p = 0.001). On the contrary, a negative correlation was detected for the level of IL-38 in sera. CONCLUSIONS: The results highlighted the systemic effect of IL-17 and the local effect of IL-38 in TAO. We observed a significant increase in the production of IL-17, and a decrease in IL-38 in samples of sera and unstimulated tears (the active form of TAO). Our data indicate a correlation of IL-17 and IL-38 levels with the clinical activity of TAO.

ITGA2 Gene Polymorphism Is Associated with Type 2 Diabetes Mellitus in the Kazakhstan Population.

Background and Objectives: Nowadays, every tenth adult in the world suffers from diabetes mellitus (DM). Diabetic retinopathy (DR) is the most common microvascular complication of type 2 DM (T2DM) and a leading cause of acquired blindness in middle-aged individuals in many countries. Previous studies have identified associations of several gene polymorphisms with susceptibility to microvascular complications of DM in various worldwide populations. In our study, we aimed to test the hypothesis of the associations of single nucleotide polymorphisms (SNP) of the VEGF (-2549I/D), RAGE (-429T/C and -374T/A), TCF7L2 (rs7903146), and ITGA2 (BglII) genes with a predisposition to DR among T2DM patients in the Kazakhstan population. Materials and Methods: We conducted a case-control study comparing the genotype distribution and allele frequencies between groups of DR patients (N = 94), diabetic patients without DR (N = 94), and healthy controls (N = 51). Genotypes were identified using the PCR-RFLP method. Results: In all cases, the genotype distribution corresponded to the Hardy-Weinberg equilibrium. The groups of diabetic patients with and without DR did not significantly differ in the genotype distribution of the SNPs studied. Differences between both groups of diabetic patients and healthy controls in four out of five SNPs were also not significant. At the same time, both groups of diabetic patients differed significantly from healthy controls in genotype distribution (p = 0.042 and 0.005, respectively) and allele frequencies (p = 0.021 and 0.002, respectively) of the BglII polymorphism in the ITGA2 gene. After adjusting for multiple comparisons, the differences between the group of diabetic patients without DR and the control group remained significant (pBonf = 0.027 for genotypes and pBonf = 0.009 for alleles). The BglII- allele was associated with diabetes: OR = 1.81 [1.09-2.99] for DR patients, and OR = 2.24 [1.34-3.75] for diabetic patients without DR. The association was also observed in the subset of Kazakhs. Conclusions: This study shows that the BglII polymorphism in the ITGA2 gene can be associated with T2DM but not with DR. According to our data, the risk allele for diabetes is the wild BglII- allele, and not the minor BglII+, which is considered as risky for DR.

FGF-23 and Phosphate in Children with Chronic Kidney Disease: A Cross-Sectional Study in Kazakhstan.

Background and objectives: Chronic kidney disease (CKD) in children is a complex medical and social issue around the world. One of the serious complications is mineral-bone disorder (CKD-MBD) which might determine the prognosis of patients and their quality of life. Fibroblast growth factor 23 (FGF-23) is a phosphaturic hormone which is involved in the pathogenesis of CKD-MBD. The purpose of the study was to determine what comes first in children with CKD: FGF-23 or phosphate. Materials and Methods: This cross-sectional study included 73 children aged 2-18 years with CKD stages 1-5. We measured FGF-23 and other bone markers in blood samples and studied their associations. Results: Early elevations of FGF-23 were identified in children with CKD stage 2 compared with stage 1 (1.6 (1.5-1.8) pmol/L versus 0.65 (0.22-1.08), p = 0.029). There were significant differences between the advanced stages of the disease. FGF-23 correlated with PTH (r = 0.807, p = 0.000) and phosphate (r = 0.473, p = 0.000). Our study revealed that the elevated level of FGF-23 went ahead hyperphosphatemia and elevated PTH. Thus, more than 50% of children with CKD stage 2 had the elevating level of serum FGF-23, and that index became increasing with the disease progression and it achieved 100% at the dialysis stage. The serum phosphate increased more slowly and only 70.6% of children with CKD stage 5 had the increased values. The PTH increase was more dynamic. Conclusions: FGF-23 is an essential biomarker, elevates long before other markers of bone metabolism (phosphate), and might represent a clinical course of disease.