Study of Association of Chromosomal Region 1Q21-23 with Rheumatoid Arthritis and Their Correlation with Severity of Disease.

BACKGROUND: The understanding of the pathophysiology of rheumatoid arthritis (RA) has taken a major step forward with the research of new illness-related genes and further deciphering the involved molecular. Gene variants like human leukocyte antigen (HLA)-DRB1 and PTPN22 1858T act as individual risk factors for RA. It also serves as a risk factor for the rate of progression of joint destruction and clinical manifestations in autoimmune diseases like RA. The focus of this study is to find out the association of chromosomal region 1q21-23 with RA and its connection with disease severity using the disease activity score (DAS) and distribution frequency of the prevalent alleles of such genes in an already recruited group of patients/controls of India, specifically Northwest Rajasthan. MATERIALS AND METHODS: This was a case-control study wherein every patient of RA aged 16 years and above diagnosed with RA as per the 2010 American College of Rheumatology (ACR) and the European League against Rheumatism (EULAR) revised criteria for RA in Outpatient Department (OPD) and Inpatient Department (IPD) patients were included. Blood samples of the study population were drawn at Sardar Patel Medical College (SPMC), Bikaner (rheumatology OPD), along with the cooperation of Birla Institute of Technology and Science (BITS), Hyderabad (Department of Biological Sciences) from July 2009 to January 2012. A total of 100 controls (without any previous history of disease) and 135 cases were selected considering inclusion and exclusion criteria. Clinical data along with laboratory parameters like complete blood count, serum electrolytes (sodium, potassium, calcium, and chlorine ions), blood sugar, blood urea with serum creatinine, lactate dehydrogenase (LDH) isoenzymes assay, serum glutamic-oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT) ratio, serum γ-glutamyl transferase (GGT) level, serum amylase, arterial blood gas (ABG), total serum proteins were evaluated and recorded from the patients. RESULTS: Our study showed control group has a mean age of 45.11 + 4.12 years. The case and control groups did not have significant differences in any of the clinical variables. 59% of cases show joint deformity. Allelic frequencies of the D1S498 polymorphism in cases were found significant in sizes 198, 204, 208, and 210, while it was found insignificant in sizes 192, 196, 200, 202, and 206. No correlation was found in allelic frequencies of the D1S318 polymorphism in cases and controls. CONCLUSION: Bigger cohort studies will allow better genomic elucidation of clinically defined intermediate phenotypes evaluated in RA patients by virtue of the autoimmune origin of the disease and its diverse symptoms in patients. Genetic-molecular studies can be a milestone for adopting effective personalized treatment for such progressively debilitating diseases. How to cite this article: Gauri LA, Meena MK, Singh U, et al. Study of Association of Chromosomal Region 1Q21-23 with Rheumatoid Arthritis and Their Correlation with Severity of Disease. J Assoc Physicians India 2023;71(9):28-32.

Role of miRNA Let-7 in Plasma of Rheumatoid Arthritis.

Objectives: Micro ribonucleic acids (miRNAs) are noncoding RNAs, recently implicated as potential biomarkers or therapeutic targets for autoimmune diseases such as rheumatoid arthritis (RA). The aim of this study is to assess the role of miRNA Let-7 in the plasma of RA. Materials and methods: Trained medical staff already enrolled for the study collected blood samples from healthy controls (N = 42) and RA patients (N = 44). In the laboratory, these samples were centrifuged at 2000 rpm for 8 minutes to separate serum from the sample, which was then transferred to a plain vial. Until transport to the genetic lab, samples were stored at -20°C Deoxyribonucleic acid (DNA) was isolated using a standard protocol cohort of controls and patient blood samples. Quantification of DNA was conducted using ultraviolet (UV) spectroscopy, and DNA quality was assessed on 0.8% agarose gel. A comparison of genotype frequencies in the different study groups was performed using the Chi-squared test, while a comparison of allelic frequencies was conducted using Fisher's exact test. Results: Variations of alleles, such as 16539423 (G>T), 16539433 (T>G), and 16539629 (A>T) were found only in RA patients. On the other hand, 16539617 (T>A), 16539622 (G>T), and 16539624 (T>C) were found only in control cases. Five sequences (three RA variants and two control variants) with minimal alignment were compared to the wild-type sequence. We found that the sequence modification of pre-miRNA 16539623 del G was significantly higher and had a risk allele in the study group [odds ratio (OR) = 3.29]. Conclusion: Rheumatoid arthritis (RA) is an autoimmune disorder that presents with a variety of clinical manifestations. Genetic factors possibly account for about 60% of disease susceptibility and expression, thus playing a very important role in disease pathogenesis. How to cite this article: Gauri LA, Liyakat N, Dadhich D, et al. Role of miRNA Let-7 in Plasma of Rheumatoid Arthritis. J Assoc Physicians India 2023;71(11):50-52.

Association of CRP Haplotypes in Rheumatoid Arthritis and their Correlation with Severity of the Disease.

BACKGROUND: Rheumatoid arthritis is a heterogenous autoimmune disorder of unknown cause with variable clinical expression. Genetic factors play an important role and likely account for about 60% of disease susceptibility and expression. The aim of this study to find out the association of CRP haplotypes in rheumatoid arthritis and their correlation with severity of the disease. MATERIAL AND METHODS: This was case control study where in all available patients and volunteers (only for blood samples) were recruited. Peripheral blood samples of patients were collected at Rheumatology Clinic and Medicine Department of S.P. Medical College, Bikaner in collaboration with Department of Biological Sciences, BITS, Pilani-Hyderabad during July 2009 to January 2012. 100 control subjects with no known history of disease and 135 cases were recruited as per pre-decided inclusion and exclusion criteria. A tag SNP approach captured common variation at the CRP locus and the relationship between genotype and serum CRP was explored by linear modelling. RESULTS: Cases comprised of 98 females (Mean age 43.01+13.23 yrs) and 37 (mean age 47.4+14.9 years) males. The Control group comprised of 100 unrelated healthy controls. The cases and controls did not differ significantly for any of the clinical parameters, except for serum CRP levels. The allele distribution of rs1205 polymorphism among the studied cases and controls, which was statistical non-significant. The rs3093066 polymorphism located at the 3` position of the gene in the UTR at position number 157949723. The rs3116640 polymorphism located at 157948938 position on chromosome1 and the allele distribution of rs3116637 polymorphism among cases and controls which was also found to be monomorphic respectively. CONCLUSION: Extending the studies to a larger cohort will also allow genetic analyses of clinically defined endophenotypes observed in the patients of this chronic metabolic disease with attributes of autoimmune disorder and multiple symptoms in patients. Genetic studies can also impact strategies adopted for effective personalized treatment for this progressively debilitating disease.

Study of Bone Mineral Density (BMD) in Patients with Rheumatoid Arthritis and its Co-relation with Severity of the Disease.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology marked by a symmetric, peripheral polyarthritis.1-3 People with rheumatoid arthritis are at increased risk of osteoporosis. Hence this article intends to highlight the importance of BMD measurement in patients with RA as a tool for assessment of disease activity and severity. OBJECTIVE: To evaluate Bone Mineral Density in patients of Rheumatoid Arthritis and Co-relate it with severity of disease. MATERIAL AND METHODS: Hand bone density was measured on the plain radiographs of the right hand using digital x-ray radiogrammetry (Pronosco Xposure System 2.0). This BMD was correlated with markers of disease activity using DAS 28 Scoring system.4. RESULTS: In our study there were 200 patients with equal number of controls. 70 patients in study group and 131 patients in control group were <45 years old and had normal Z-score while in age group >45 years 26 and 20 cases in study and control groups respectively had their Z-score within normal range. There were total 21 and 2 cases of study and control groups respectively (age <45 years) who had osteoporosis while in age group >45 years 12 and 10 cases in study and control groups respectively had osteopenia. CONCLUSIONS: Patients with RA are more susceptible for bone loss in comparison to normal age and gender related subjects. Patients with longer duration and higher disease activity are more susceptible for developing osteopenia and osteoporosis. Occurrence of joint deformities increases with longer disease duration. Limitation of physical activity impairs the bone mineral density. Patient taking anti-rheumatic therapy (steroids and Disease-modifying antirheumatic drugs) are at increased risk of bone loss. All these factors contribute to bone loss independent of each other.