Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 21 5 2022 10 26 537 548 EN Zhenzhen Su Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China Lin Chen Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, China Qian Niu Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China Bin Yang Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China Zhuochun Huang Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China 2021 10 27 2022 07 06 Rheumatoid arthritis (RA) is caused by complicated interactions between genes and the environment. CXC chemokine receptor 5 (CXCR5) is required for B and T follicular helper cell migration and humoral immunity generation. Therefore, this study aimed to assess whether polymorphisms of the CXCR5 gene are implicated in RA development and progression. This case-control study enrolled 285 RA patients and 291 healthy controls. The polymerase chain reaction-ligase detection reaction method was used to genotype rs630923, rs497916, rs3922, and rs676925 in the CXCR5 gene. Epidemiological, clinical, and laboratory data were collected retrospectively. The rs630923 A allele was associated with a higher risk of RA (AOR [adjusted odds ratio]=2.00, 95% confidence interval [CI] =1.14–3.53). However, in the RA group, the frequency of the rs497916 T allele was lower (AOR=0.69, 95% CI=0.51–0.93). Regarding rs3922, AG+GG genotype carriers were at a significantly lower risk for RA than AA genotype carriers (AOR=0.70, 95% CI=0.49–0.99). In the RA group, we found that the different genotypes were significantly associated with specific laboratory values, including rheumatoid factor, total bilirubin, total cholesterol, low-density lipoprotein cholesterol, and alkaline phosphatase. This is the first report indicating that CXCR5 polymorphisms were associated with RA susceptibility. These findings lead to a rising possibility of identifying RA-susceptible individuals based on genetic markers. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3390 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3390/1881