Different Contributions of CDKAL1, KIF21B, and LRRK2/MUC19 Polymorphisms to SAPHO Syndrome, Rheumatoid Arthritis, Ankylosing Spondylitis, and Seronegative Spondyloarthropathy.
OBJECTIVES
Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, rheumatoid arthritis (RA), ankylosing spondylitis (AS), and seronegative spondyloarthropathy (SPA) are autoimmune diseases of unknown etiology, which share some clinical manifestations in common. Previous family-based investigations support genetic contributions to the susceptibility of these diseases. The current study evaluated whether three previously reported AS-associated single-nucleotide polymorphisms (SNPs), rs6908425 T>C in CDKAL1, rs11584383 T>C near KIF21B, and rs11175593 C>T near LRRK2/MUC19, have any genetic overlap across multiple autoimmune diseases including SAPHO syndrome, RA, AS, and SPA.


MATERIALS AND METHODS
Genomic DNA was obtained from 71 SAPHO, 125 RA, 67 AS, and 35 SPA Han Chinese patients, as well as 104 healthy controls. SNPs were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Genotype and allele frequencies were analyzed using chi-square test.


RESULTS
rs6908425 T>C in CDKAL1 was significantly different between SAPHO cases and healthy controls (odds ratios = 2.056, 95% confidence intervals: 1.211-3.490; p = 0.007), but no SNPs were associated with the risk of developing RA, AS, or SPA (p > 0.05). Analysis of genotype distributions showed similar results. A significant difference was only found in the genotype frequency of rs6908425 in SAPHO cases (p = 0.004); no significant differences were detected among patients with RA, AS, and SPA (p > 0.05).


CONCLUSIONS
Our results suggest that rs6908425 in CDKAL1 is associated with the risk of developing SAPHO in Han Chinese populations. People who carry the risk allele T of rs6908425 might be more prone to developing SAPHO syndrome.
['Li|Nan|N|', 'Ma|Junfen|J|', 'Li|Kai|K|', 'Guo|Changlong|C|', 'Ming|Liang|L|']
D020083:Acquired Hyperostosis Syndrome D000328:Adult D000368:Aged D000483:Alleles D001172:Arthritis, Rheumatoid D016022:Case-Control Studies D005006:Ethnicity D005260:Female D005787:Gene Frequency D020022:Genetic Predisposition to Disease D006801:Humans D016547:Kinesins D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 D008297:Male D008875:Middle Aged D020641:Polymorphism, Single Nucleotide D025242:Spondylarthropathies D013167:Spondylitis, Ankylosing D012359:tRNA Methyltransferases
CDKAL1 polymorphism SAPHO syndrome Rs6908425