Role of HLA-DRB1, PTPN22, CTLA4 Gene Polymorphisms in Susceptibility to Rheumatoid Arthritis
Journal Title: Journal of Medical Science And clinical Research - Year 2016, Vol 4, Issue 7
Abstract
Background and AIM: The genetic and environmental factors are believed to play an important role in the pathogenesis of rheumatoid arthritis (RA), the precise etiology is still uncertain. Regarding its genetic components, the strongest genetic association with RA is that found for certain alleles of HLA-DRB1. Recent studies have revealed that the single‐nucleotide polymorphism (SNP) of non-HLA PTPN22 and CTLA4 gene were associated with RA. The associations of HLA, PTPN22 and CTLA4 polymorphisms with RA risk have been less well replicated. Thus, the current study was undertaken to investigate the effects of HLA-DRB1, PTPN22, CTLA4 gene polymorphisms and autoantibodies in susceptibility to RA. Methods: A total of 200 patients fulfilled the criteria for RA and 200 healthy individuals were included in the study. Anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF) were measured by enzyme-linked immunosorbent assay (ELISA). HLA-DRB1 alleles were determined by polymerase chain reaction-sequence specific primer (PCR-SSP) method. Samples were genotyped for PTPN22 1858C/T (rs2476601) and CTLA4 CT60 (rs3087243) variants using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: In RA patients 88% and 82% were positive for anti-CCP and RF autoantibodies, respectively. A significant increase in the frequency of HLA-DRB1*01, HLA-DRB1*04, HLA-DRB1*10, HLA-DRB1*14 shared epitope (SE) alleles were identified in RA patients, whereas in healthy subjects, they were HLADRB1*03, HLA-DRB1*07, HLA-DRB1*11, HLA-DRB1*13. There was no association of the PTPN22 1858T variant with RA and it seems to be independent of MHC associations. The frequency of CTLA4 CT60 A allele carriers was significantly higher in RA patients and also it is preferentially in SE-positive RA patients. Conclusion: Our results confirmed the previously reported HLA-DRB1 SE alleles associations with RA. The CTLA4 polymorphism appears to interfere with HLA-DRB1 susceptibility to RA. On the other hand, we failed to provide evidence for the association of the PTPN22 SNP with RA.
Authors and Affiliations
Vasanth Konda Mohan
Comparison of Abdominal, Vaginal and Non Descent Vaginal Hysterectomy: Perioperative Outcome
Introduction: Hysterectomy is the commonest major gynaecological surgery performed in women. Currently there are three main types of hysterectomy operations –abdominal hysterectomy (AH), vaginal hysterectomy (VH) and non...
Guidelines for Medico Legal Certification with Review of Statutes
The term ‘MLC’ (Medico legal case) has been creating mayhem in the minds of millions of medical practitioners for years, and will continue to do for years to come. Even today, the term fails to find a place neither in th...
An Evaluation of the Metabolic Parameters in Women with Gestational Diabetes Mellitus after Delivery
Objective: To evaluate the metabolic parameters in women with gestational diabetes mellitus after delivery in north Indian women. Methods: This was a comparative study. A total of 50 patients were included in the study....
Nasal Polyps- Causes and Associated Symptoms- A Clinical Study
Background: Nasal polyps (NP) are mucosal lesions of the nasal or paranasal sinuses that can result from a response to inflammatory or infectious stimuli. The present study was conducted to determine the causes and occur...
A Prospective, Randomized, Double blinded, Comparative Study of Clonidine and Tramadol for Control of Shivering under Spinal Anesthesia
BACKGROUND: Shivering is a common complication of spinal anesthesia. We compared the efficacy of intravenous clonidine and tramadol for the treatment of shivering under spinal anesthesia. MATERIALS AND METHODS: In this p...