Interaction analysis between <i>BLK</i> rs13277113 polymorphism and <i>BANK1</i> rs3733197 polymorphism, <i>MMEL1/TNFRSF14</i> rs3890745 polymorphism in determining susceptibility to rheumatoid arthritis
Creators: name: Huang, Hua
name: Huang, Si-Chao
name: Hua, Dong-Jin
name: Sun, Qing-Qing
name: Cen, Han
name: Xin, Xia-Fei
Publisher: name: Taylor & Francis
Year: 2017
Subjects: subject: Biophysics
subject: Genetics
subject: FOS: Biological sciences
subject: Physiology
subject: Environmental Sciences not elsewhere classified
subject: Ecology
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Developmental Biology
subject: Cancer

description: Two pairwise genetic interactions (<i>B cell lymphocyte kinase</i> (<i>BLK</i>) rs13277113,<i>B cell scaffold protein with ankyrin repeats 1</i> (<i>BANK1</i>) rs3733197and <i>BLK</i> rs13277113 <i>membrane metalloendopeptidase like 1</i> (<i>MMEL1</i>)/ <i>tumor necrosis factor receptor superfamily member 14</i> (<i>TNFRSF14</i>) rs3890745) have been demonstrated in determining susceptibility to rheumatoid arthritis (RA) without replication, thus this study was performed to examine whether abovementioned genetic polymorphisms were associated with RA and further tests were performed to see whether aforementioned genetic interactions existed in RA among Chinese population. A total of 328 patients with RA and 449 healthy control subjects were included in the current study. The polymorphisms were genotyped using the ligase detection reaction-polymerase chain reaction (LDR-PCR) technology. The association of RA with each polymorphism was analyzed by multivariate logistic regression model. Interaction analysis was done by multiple methods. Significant difference in genotype distribution of <i>BLK</i> rs13277113 polymorphism between RA patients and healthy controls was found (<i>p</i> = 1.01 × 10<sup>−2</sup>). The major allele A of <i>BLK</i> rs13277113 polymorphism was significantly increased in RA patients compared with controls (OR = 1.36, 95% CI = 1.08–1.71, <i>p</i> = 9.27 × 10<sup>−3</sup>). Significant association of RA with the major allele A of <i>BLK</i> rs13277113 polymorphism under dominant model was also detected (OR = 2.74, 95% CI = 1.42–5.29, <i>p</i> = 2.73 × 10<sup>−3</sup>). However, we did not find significant association between neither <i>BANK1</i> rs3733197 polymorphism nor <i>MMEL1/TNFRSF14</i> rs3890745 polymorphism and RA. Non-significant evidence was found for neither additive nor multiplicative interaction for these two pairwise genetic polymorphisms (<i>BLK</i> rs13277113-<i>BANK1</i> rs3733197; <i>BLK</i> rs13277113<i>-MMEL1/TNFRSF14</i> rs3890745). Significant association of RA with G allele of <i>BANK1</i> rs3733197 polymorphism was only found among individuals carrying A/A genotype of the <i>BLK</i> rs13277113 polymorphism (OR = 1.49, 95% CI = 1.01–2.18, <i>p</i> = .04). In summary, our results indicated that the <i>BLK</i> rs13277113 polymorphism was involved in the genetic background of RA in Chinese population and the association of <i>BANK1</i> rs3733197 polymorphism with RA was dependent on the genotype of <i>BLK</i> rs13277113 polymorphism, highlighting B-cell response implicated in the pathogenesis of RA.