Neuropsychiatric systemic lupus erythematosus is associated with imbalance in interleukin 10 promoter haplotypes

Abstract

Objective-To investigate the association of interleukin 10 (IL10) promoter polymorphisms and neuropsychiatric manifestations of systemic lupus erythematosus (SLE). Methods-IL10 haplotypes of 11 healthy volunteers were cloned to confirm that in the Dutch population, only the three common haplotypes (-1082/-819/-592) GCC, ACC and ATA exist. The IL10 promoter polymorphisms of 92 SLE patients and 162 healthy controls were determined. The medical records of the SLE patients were screened for the presence of neuropsychiatric involvement. Results-All cloned haplotypes were either GCC, ACC or ATA. Forty two SLE patients had suVered from neuropsychiatric manifestations (NP-SLE). In NP-SLE patients, the frequency of the ATA haplotype is 30% versus 18% in the controls and 17% in the non-NP-SLE group (odds ratios 1.9, p=0.02, and 2.1, p=0.04, respectively), whereas the GCC haplotype frequency is lower in the NP-SLE group compared with controls and non-NP-SLE patients (40% versus 55% and 61%, odds ratios 0.6, p=0.02 and 0.4 p=0.006). The odds ratio for the presence of NP-SLE is inversely proportional to the number of GCC haplotypes per genotype when the NP-SLE group is compared with non-NP-SLE patients. Conclusions-The IL10 locus is associated with neuropsychiatric manifestations in SLE. This suggests that IL10 is implicated in the immunopathogenesis of neuropsychiatric manifestations in SLE. (Ann Rheum Dis 1999;58:85-89) Genetic factors play an important part in the aetiopathogenesis of systemic lupus erythematosus (SLE). This is illustrated by the 50-60% concordance rate of SLE beween monozygotic twins.1 Furthermore, several susceptibility loci have been identified, including HLA class I and II, C4A complement null alleles, tumour necrosis factor (TNF), and Fc--RIIIa polymorphisms. [2][3][4][5][6]

Interleukin-10 promoter polymorphism in sporadic Alzheimer's disease

“…45 Interestingly, then, the IL-10 ATA haplotype is associated with neuropsychiatric manifestations in SLE. 46 Data herein reported demonstrate that the percentage of À1082A carrier subjects is significantly increased among AD patients and this increase is mainly due to increase of the ATA haplotype. We were unable to find differences in IL-10 allele distribution among AD patients carrying the E4 allele or not.…”

Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5′ regulatory region

“…Our results are in agreement with previous studies in different populations failing to detect an association with SLE susceptibility of five SNPs located at positions À3533, À2828, À1082, À819 and À592 19,[26][27][28]34 although a role in the clinical phenotype was suggested. 26,27,35 Conversely, the SNP at position À2726 (named À2763 in Ref. 19) was found to be associated with SLE susceptibility in a group of African-American patients.…”

Interleukin-10 Therapy—Review of a New Approach

“…The strongest association seems to be established for SLE, where it has been suggested that high IL-10 expression (Llorente et al, 1995(Llorente et al, , 1997, and the corresponding IL-10 alleles (Eskadale et al, 1997b), play a causative or aggravating role Gonzalez-Amaro et al, 1998;Rood et al, 1999). The IL10.G microsatellite showed significant allele skewing in patients versus controls.…”