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

doi:10.1136/ard.58.2.85

Annals of the Rheumatic Diseases 1999;58:85-89; doi:10.1136/ard.58.2.85

Ann Rheum Dis 1999;58:85-89 ( February )

Extended reports

Neuropsychiatric systemic lupus erythematosus is associated with imbalance in interleukin 10 promoter haplotypes M J Rood,^a V Keijsers,^a M W van der Linden,^b T Q T Tong,^a S E Borggreve,^a C L Verweij,^a F C Breedveld,^a T W J Huizinga^a

^a Departments of Rheumatology, ^b and Clinical Epidemiology, ^c Leiden University Medical Centre, Leiden, the Netherlands

Correspondence to: Dr T W J Huizinga, Leiden University Hospital, Department of Rheumatology, C4-R, PO Box 9600, 2300 RC Leiden, the Netherlands.

Accepted for publication 2 November 1998

OBJECTIVE $---$ To investigate the association of interleukin 10 (IL10) promoter polymorphisms and neuropsychiatric manifestations of systemiclupus 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 polymorphismsof 92 SLE patients and 162 healthy controls were determined. Themedical records of the SLE patients were screened for the presenceof neuropsychiatricinvolvement.
RESULTS $---$ All cloned haplotypes were either GCC, ACC or ATA. Forty two SLE patients had suffered from neuropsychiatric manifestations(NP-SLE). In NP-SLE patients, the frequency of the ATA haplotypeis 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), whereasthe GCC haplotype frequency is lower in the NP-SLE group comparedwith 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 thepresence of NP-SLE is inversely proportional to the number ofGCC haplotypes per genotype when the NP-SLE group is comparedwith non-NP-SLEpatients.
CONCLUSIONS $---$ The IL10 locus is associated with neuropsychiatric manifestations in SLE. This suggests that IL10 is implicated in the immunopathogenesisof neuropsychiatric manifestations inSLE.

Keywords: systemic lupus erythematosus; neuropsychiatric manifestations; genetics; interleukin 10 promoter haplotypes

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