Department of Physical Examination, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang, PR China.
Department of Preventive Medicine, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
Int Immunopharmacol. 2021 Apr;93:107378. doi: 10.1016/j.intimp.2021.107378. Epub 2021 Jan 30.
This study was performed to test whether ATG16L1 rs2241880, rs6758317 and ATG16L2 rs11235604 polymorphisms were associated with RA and further examine the genetic interaction between ATG16L1 and ATG16L2 in RA among a Chinese population.
A total of 594 RA patients and 604 healthy controls were included, and the genetic polymorphisms were genotyped based on HI-SNP technology.
Significant associations of ATG16L1 rs2241880 polymorphism with RA (T/T versus C/T + C/C, OR = 1.32, 95% CI 1.04-1.67, P = 0.02), cyclic citrullinated peptide (CCP)-positive RA (genotype comparison, P = 5.38 × 10; T/T versus C/T + C/C, OR = 1.45, 95% CI 1.12-1.87, P = 4.86 × 10) and rheumatoid factor (RF)-positive RA (genotype comparison, P = 0.03; T versus C, OR = 1.23, 95% CI 1.01-1.49, P = 0.04; T/T versus C/T + C/C, OR = 1.44, 95% CI 1.10-1.88, P = 7.62 × 10) were found. Significant genetic interaction between ATG16L1 rs2241880 and ATG16L2 rs11235604 was associated RA (P = 0.03), and significant genetic interaction between ATG16L1 rs6758317 and ATG16L2 rs11235604 was associated with RA (P = 7.57 × 10), CCP-positive RA (P = 0.01) and RF-positive RA (P = 0.01). Consistently, stratification analysis found that significant associations of RA with ATG16L1 rs2241880, rs6758317 polymorphisms were only detected among individuals carrying C/T genotype of the ATG16L2 rs11235604 polymorphism.
Our results indicated that ATG16L1 rs2241880 polymorphism was associated with RA in Chinese population, and provided evidence for genetic interaction between ATG16L1 and ATG16L2 in determing the development of RA, highlighting the involvement of autophagy in the pathogenesis of RA.
本研究旨在检验 ATG16L1 rs2241880、rs6758317 和 ATG16L2 rs11235604 多态性是否与类风湿关节炎（RA）相关，并进一步探讨中国人群中 ATG16L1 和 ATG16L2 之间的遗传相互作用。
共纳入 594 例 RA 患者和 604 例健康对照者，采用 HI-SNP 技术对这些基因多态性进行基因分型。
ATG16L1 rs2241880 多态性与 RA（TT 与 CT+C 相比，OR=1.32，95%CI 1.04-1.67，P=0.02）、环瓜氨酸肽（CCP）阳性 RA（基因型比较，P=5.38×10；TT 与 CT+C 相比，OR=1.45，95%CI 1.12-1.87，P=4.86×10）和类风湿因子（RF）阳性 RA（基因型比较，P=0.03；T 与 C 相比，OR=1.23，95%CI 1.01-1.49，P=0.04；TT 与 CT+C 相比，OR=1.44，95%CI 1.10-1.88，P=7.62×10）显著相关。ATG16L1 rs2241880 与 ATG16L2 rs11235604 之间存在显著的遗传相互作用与 RA（P=0.03）相关，ATG16L1 rs6758317 与 ATG16L2 rs11235604 之间存在显著的遗传相互作用与 RA（P=7.57×10）、CCP 阳性 RA（P=0.01）和 RF 阳性 RA（P=0.01）相关。分层分析发现，仅在 ATG16L2 rs11235604 携带 CT 基因型的个体中，ATG16L1 rs2241880 和 rs6758317 多态性与 RA 显著相关。
本研究结果表明，在中国人群中，ATG16L1 rs2241880 多态性与 RA 相关，并为 ATG16L1 和 ATG16L2 之间在决定 RA 发病机制中的遗传相互作用提供了证据，强调了自噬在 RA 发病机制中的作用。
