Genetic Variations in TGF-B1 and MTHFR in Osteoarthritis Patients and Healthy Controls

Research Article

Austin Arthritis. 2023; 4(1): 1017.

Genetic Variations in TGF-β1 and MTHFR in Osteoarthritis Patients and Healthy Controls

Vishal Chandra1; Tashfeen Ashraf MD2; Pramod Yadav1,3*; Vikas Raghuvanshi1,4

1School of Life Sciences and Biotechnology, Chhatrapati Shahu Ji Maharaj University Kanpur, Uttar Pradesh, India

2School of Biotechnology, Gautam Buddha University, Greater Noida, India

3Department of AFAF, Amity University Uttar Pradesh, India

4Madurai Kamaraj University, Tamil Nadu, India

*Corresponding author: Pramod Yadav Department of AFAF, Amity University Uttar Pradesh, Noida Campus, 201313, India. Email: pramodyadavk3@gmail.com

Received: October 25, 2023 Accepted: November 28, 2023 Published: December 05, 2023

Abstract

Background: The objective of this study was to compare the genomic features of TGF-β1 and MTHFR between patients with Osteoarthritis (OA) and healthy controls in Kanpur, India.

Methods: This study collected blood samples from 220 participants, including 100 OA patients and 120 healthy individuals, and analysed them use genetic polymorphism analysis techniques. The differences in the genetic makeup of TGF-β1 and MTHFR genes between the two groups were determined by using PCR techniques and statical analysis.

Results: The results showed significant variations in the expression levels of the TGF-β1 gene in OA patients compared to healthy controls, suggesting its potential role in the pathogenesis of OA. However, the MTHFR 1298A>C SNP was not significantly associated with OA disease in any genetic model, indicating that it is not associated with the pathogenesis of OA.

Conclusions: This study highlights the importance of further research to investigate the underlying mechanisms of TGF-β1 and MTHER, and its potential as a therapeutic target for the disease.

Keywords: Pathogenesis; Therapeutic targets; Genomic comparison; TGF-β1; MTHFR

Abbreviations: OA: Osteoarthritis; TGF-β1: Transforming Growth Factor-beta 1; MTHFR: Methylenetetrahydrofolate Reductase; SNP: Single Nucleotide Polymorphism; PCR: Polymerase Chain Reaction; CI: Confidence Interval; OR: Odds Ratio; BMI: Body Mass Index; HAQ: Health Assessment Questionnaire; DAS-28: Disease Activity Score 28; CRP: C-reactive Protein; ECM: Extracellular Matrix; K-L: Kellgren and Lawrence; VAS: Visual Analog Scale; ACR: American College of Rheumatology; DNA: Deoxyribonucleic Acid; PCR: Polymerase Chain Reaction; ARMS PCR: Amplification Refractory Mutation System Polymerase Chain Reaction; CT: Cytosine to Thymine; AT: Adenine to Thymine; SNPs: Single Nucleotide Polymorphisms; BP: Blood Pressure

Introduction

With more than 100 million people worldwide, Osteoarthritis (OA) is a prevalent rheumatologic disorder that usually affects the joints of hands, feet, knees, and hips. The prevalence rates of knee OA range from 7.5% (in China) to 25% (in northern Pakistan) and 22-39% in India, where it is the second most common rheumatologic problem [1,2]. The degeneration of cartilage occurs due to the direct rubbing of bones during movement and it causes pain, discomfort, swelling, and loss of motion [1,3]. Knee OA is worst affected in people aged 65 years and above [4]. The exact pathogenesis behinds OA remains unclear, but it is believed that it is a multifactorial disease influenced by both genetic and environmental factors. Several genes have been implicated in the development of OA and it accounts for more than 20% of OA's heritability. Most of them are located in noncoding regions of the genome, where they are presumed to regulate the expression of target genes [5,6]. Cartilage DNA methylation changes in cis have been shown to correlate with a large number of risk variants which indicate that epigenetics may play a role in MTHER gene expression [1]. Among the genetic factors, transforming growth factor-beta 1 (TGF-β1) and Methylenetetrahydrofolate Reductase (MTHFR) are two important genes that have been implicated in OA susceptibility and progression [7]. Studies have shown that TGF-β1 signalling is required for the formation of articular cartilage during early joint development but may also be involved in joint destruction [7]. Additionally, TGF-β has been implicated in abnormal bone remodelling and cartilage degeneration in OA [8,9]. Genetic variations of the MTHFR gene link to the incidence of spinal osteophyte formation [10]. However, studies report conflicting results on whether MTHFR gene polymorphism is associated with early primary knee osteoarthritis or not [11]. The present study is an important addition to the ongoing research on osteoarthritis, specifically by focusing on the Kanpur District of Uttar Pradesh State in India. The primary objective of the study is to investigate the association of TGF-β1 and MTHFR genes with OA disease, as well as to explain the amplification of PCR and polymorphism of these genes. The results of this study are expected to be useful for the pharmaceutical industry in developing new medications for OA.