title: Influence of BLK polymorphisms on the risk of rheumatoid arthritis.
abstract: B cell lymphocyte kinase (BLK) encodes a member of the Src kinase family and thus may influence the proliferation and differentiation of cells. A single nucleotide polymorphism (SNP) located in the first intron of BLK has shown that the risk C allele of rs2248932 is associated with lower levels of messenger RNA expression of BLK. We hypothesized that this polymorphism may contribute to rheumatoid arthritis (RA) susceptibility. We studied BLK rs2248932 T/C gene polymorphisms in 329 patients with RA and 697 controls in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). When the BLK rs2248932 TT homozygote genotype was used as the reference group, the CC genotype was associated with a significantly increased risk of RA. In the recessive model, when the BLK rs2248932 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significantly increased susceptibility to RA. In stratification analyses, a significantly increased risk for RA associated with the BLK rs2248932 CC genotype was evident among younger patients, CRP-negative patients and anti-CCP-positive patients compared with the BLK rs2248932 TT/TC genotype. The risk was also significantly evident among RF-positive patients, patients with lower ESR levels, patients with lower or higher DAS28 score and patients with a lower functional class. These findings suggested that the functional SNP BLK rs2248932 T/C variant allele was associated with RA development. However, our results were obtained from a moderate-sized sample, and therefore this is a preliminary conclusion. Validation in a larger study from a more diverse ethnic population is needed to confirm these findings.
authors: Department of Orthopedics, Changzhou Second People's Hospital, Affiliated Hospital of Nanjing Medical University, Changzhou 213003, China.
authors: Hui
authors: H
authors: Zhang
authors: Liqun
authors: L
authors: Wang
authors: Yong
authors: Y
authors: Huang
authors: Chao
authors: C
authors: Zhuang
authors: Gongyin
authors: G
authors: Zhao
authors: Ruiping
authors: R
authors: Liu
authors: Yong
authors: Y
authors: Wang
mesh_terms: D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019061:src-Family Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: C082599:protein-tyrosine kinase p55(blk); D019061:src-Family Kinases