Association of interleukin 10 promoter polymorphisms with systemic lupus erythematosus

by Chong, Wai-po

Abstract (Summary)
(Uncorrected OCR) Abstract of thesis entitled

Association of interleukin 10 promoter polymorphisms with systemic lupus erythematosus

submitted by


for the Degree of Master of Philosophy at the University of Hong Kong

in September 2003

Different lines of evidence suggest that IL-10 is a candidate gene in systemic lupus erythematosus (SLE) susceptibility. (1) It maps at chromosomal region lq31-32, which is a region that was shown to be associated with SLE. (2) Hyperactivity of B cells and autoantibodies production are the hall mark of SLE and IL-IO activates B cells and promotes antibodies production. (3) Serum IL-IO level is elevated in SLE patients and correlates with disease activity. (4) Anti-IL-IO treatment can delay the disease onset and enhance survival rate for murine lupus model.

Previous studies showed that IL-lO level is associated with different promoter haplotypes, so we aimed to study the genetic association of IL-10 promoter polymorphisms with SLE in Hong Kong Chinese patients.

We performed a case-control association study of 6 single nucleotide polymorphisms (SNPs) (-3575T/A, -2849G/A, -2763C/A, -1082G/A, -8l9C/T and -592C/A) and two micro satellites, IL10.R and IL10.G in the promoter region with SLE. Our study population included 554 SLE patients and 708 healthy controls. Two of the polymorphisms, -2849G/A and IL10.R, were found to be non-polymorphic, i.e. only allele G and IL 1 0.R2 were found in our population. We concluded that these two polymorphisms are extremely rare (frequency < 0.005) or do not exist in Hong Kong Chinese.

Six haplotypes were identified without any ambiguous phasing due to complete linkage disequilibriums (LDs) among these SNPs. The frequency of the genotype of homozygous high IL-lO expression haplotype, non-htl (non -3575A/ -2849G/ -2763C/ -1082A/ -8l9T/ -592A haplotype), was found to be significantly increased in patients (P= 0.009, OR= 1.801, 95% CI: 1.152 to 2.815). Fifteen different alleles were found in IL10.G. They ranged from ILlO.G3 (CA repeat number=15) to ILlO.G17 (CA repeat number=29). Among them, the frequency of ILlO.G4 (CA repeat number=16) was significantly higher in the patients (P= 0.016, OR= 2.486, 95% CI: 1.180-5.238). For further analysis, we divided these 15 alleles into short (CA repeat number is less than or equal to 21) and long (CA repeat number is greater than 21) allele and combined them with the six haplotypes. We found that the

homozygous non-htl combined with short allele of ILlO. G has a dose-dependent effect on the susceptibility of SLE: non-htl/non-htl together with homozygous short allele showed a higher odds ratio (OR=4.11, P=0.018) than the genotype of nonhtl/non-htl with heterozygous short and long allele (OR=2.98, P=O.013) and homozygous long allele (OR=1.05, P=0.848).

We also investigated the association of IL-l 0 promoter haplotypes with SLE clinical features. The frequency of non-htl was increased in patients with serositis (P< 0.0001, OR= 2.422,95% CI 1.545-3.798).

We concluded that the high expression promoter genotype is associated with SLE. However, the function of ILlO.G and how it interacts with other SNPs to affect the IL-IO production level is still unclear. Further functional studies should be performed to investigate the association of IL-lO promoter haplotypes with IL-IO production level.

Bibliographical Information:


School:The University of Hong Kong

School Location:China - Hong Kong SAR

Source Type:Master's Thesis

Keywords:interleukin 10 lupus erythematosus genetic aspects


Date of Publication:01/01/2004

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