title: Single nucleotide polymorphisms in genes encoding toll-like receptors 7, 8 and 9 in Danish patients with systemic lupus erythematosus.
abstract: Several studies indicate a role for toll-like receptors (TLRs) in the pathogenesis of systemic lupus erythematosus (SLE). We aimed to investigate the risk of SLE and typical clinical and serological manifestations of SLE potentially conferred by selected single nucleotide polymorphisms (SNPs) of genes encoding TLR7, TLR8, and TLR9. Using a multiplexed bead-based assay, we analyzed eight SNPs in a cohort of 142 Danish SLE patients and a gender-matched control cohort comprising 443 individuals. Our results showed an association between the rs3853839 polymorphism of TLR7 and SLE (G vs. C, P = 0.008, OR 1.60, 95 % CI 1.12-2.27 in females; P = 0.02, OR 4.50, 95 % CI 1.18-16.7 in males) confirming recent findings in other populations. Additionally, an association between the rs3764879 polymorphism of TLR8 and SLE (G vs. C, P < 0.05, OR 1.36, 95 % CI 0.99-1.86 in females; P = 0.06, OR 4.00, 95 % CI 0.90-17.3 in males) was found. None of the other investigated SNPs were associated with SLE but several SNPs were associated with clinical and serological manifestations. In summary, a previously shown association between the rs3853839 SNP of TLR7 and SLE in Asian patients was also found in Danish patients. Together with the association of several other SNPs of TLR8 and TLR9 with various clinical and serological manifestations of SLE these findings corroborate the pathogenic significance of TLRs in SLE.
authors.affiliation: Institute for Inflammation Research, Department of Infectious Medicine and Rheumatology, Rigshospitalet, Copenhagen, Denmark, chrej@hotmail.com.
authors.forename: C
authors.initials: C
authors.lastname: Enevold
authors.forename: C H
authors.initials: CH
authors.lastname: Nielsen
authors.forename: R S
authors.initials: RS
authors.lastname: Jacobsen
authors.forename: M L F
authors.initials: ML
authors.lastname: Hermansen
authors.forename: D
authors.initials: D
authors.lastname: Molbo
authors.forename: K
authors.initials: K
authors.lastname: Avlund
authors.forename: K
authors.initials: K
authors.lastname: Bendtzen
authors.forename: S
authors.initials: S
authors.lastname: Jacobsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D015331:Cohort Studies; D003718:Denmark; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051199:Toll-Like Receptor 7 / Q000235:genetics*; D051200:Toll-Like Receptor 8 / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: C495348:TLR7 protein, human; C495349:TLR8 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9