Molecular Analysis of Ctla4 Gene in Patients With Behcet's Disease From an Iranian Northwest Azeri Population Publisher



Abbaspouraghdam S^{1, 2} ; Ahmadi M^{3, 4} ; Aslani S⁵ ; Daneshmandpour Y^{4, 6} ; Mehdizadeh A⁷ ; Valizadeh H⁸ ; Kamrani A² ; Khabbazi A⁹ ; Roshangar L³ ; Babaloo Z^{1, 2} Show Affiliations
Source: Gene Reports Published:2020

Abstract

Behcet's disease (BD) is an autoinflammatory disease caused by several genetic, epigenetic, immunologic, and environmental factors. This study aimed to evaluate the association between CTLA4 gene +49A/G polymorphism and risk as well as clinical manifestations of BD in the Iranian Northwest Azeri population. In this study, 47 BD patients and 61 healthy controls were enrolled. CTLA4 gene +49A/G genotyping was conducted via the tetra-primer amplification refractory mutation system–polymerase chain reaction (T-ARMS–PCR). CTLA-4 gene expression was determined by Real-time PCR and the serum level of CTLA-4 protein (sCTLA-4) was evaluated by ELISA. The A allele (OR = 3.133, 95%CI = 1.53–5.59, P = 0.005) and AA genotype (OR = 5.54, 95% CI = 2.48–13.10, P < 0.001) indicated significantly different frequency between patient and control groups. No statistically significant differences were observed between males and females regarding the genotype or allele frequency. The mRNA expression (P = 0.0002) and serum concentration (P = 0.035) of CTLA-4 were decreased in BD patients in comparison to controls. Moreover, BD patients with AA genotype showed reduced CTLA-4 gene expression (P = 0.0004) and sCTLA-4 concentration (P = 0.02) in patients compared to controls. In addition, AA genotype was associated with the severe clinical manifestations of BD. In conclusion, our study proposes that the AA genotype of the CTLA4 gene +49A/G polymorphism is an important genetic risk factors that can affect BD symptom severity in the Iranian Azari population. But these findings require further studies with larger sample sizes. © 2020