Interleukin-10 polymorphisms in Spanish IgA deficiency patients: a case-control and family study

BACKGROUND: IgA deficiency (IgAD) is the most common primary immunodeficiency in Caucasians. Genetic and environmental factors are suspected to be involved in the development of the disease. Interleukin-10 (IL-10) is a cytokine with stimulatory activity on immunoglobulin production and it may be an important regulator in IgAD pathogenesis. The IL-10 gene contains several single nucleotide polymorphisms (SNPs) and two polymorphic microsatellites located in the 5'-flanking region. Our aim was to ascertain if any of these polymorphic markers are associated or linked to IgAD in Spanish patients. METHODS: We genotyped 278 patients with IgAD and 573 ethnically matched controls for the microsatellites IL-10R and IL-10G and for three single nucleotide polymorphisms at positions -1082, -819 and -592 in the proximal promoter of the gene. We also included in this study the parents of 194 patients in order to study the IL-10 haplotypes transmitted and not transmitted to the affected offspring. RESULTS: The only allele where a significant difference was observed in the comparison between IgA deficiency patients and controls was the IL-10G12 allele (OR = 1.58 and p = 0.021). However, this p value could not withstand a Bonferroni correction. None of the IL-10R or promoter SNP alleles was found at a different frequency when patients were compared with controls. CONCLUSION: Our data do not show any significant difference in IL-10 polymorphism frequencies between control and IgAD patient samples. Their haplotype distribution among patients and controls was also equivalent and therefore these microsatellites and SNPs do not seem to influence IgAD susceptibility

1.5 Decades Later: Bearing fruits from the ACR/EULAR exchange Program

Imaging Science & TechnologyApplied Science

Association of Interleukin-10 A-592C Polymorphism in Taiwanese Children with Kawasaki Disease

Elevated serum levels of interleukin-10 (IL-10) have been reported in patients with Kawasaki disease (KD). IL-10 reduces the inflammatory actions of macrophages and T cells and it may play a significant role in the regulation of inflammatory vascular damage associated with systemic vasculitis. The aim of this study was to examine whether -592 IL-10 promoter polymorphism is a susceptibility or severity marker of KD in Chinese patients in Taiwan. The study included 105 KD patients and 100 normal controls. Genotype and allelic frequencies for the IL-10 gene polymorphism in both groups were compared. There were no significant between-group differences in the genotype distribution of IL-10 A-592C gene polymorphism (P=0.08). However, the frequency of the -592*A allele was significantly increased in the patients with KD compared with controls (71.9% vs. 61.0%, P=0.019). The odds ratio for developing KD in individuals with IL-10-592*A allele was 1.64 (95% confidence interval, 1.06-2.52) compared to individuals with the IL-10-592*C allele. No significant difference was observed in the genotype and allelic frequencies for the IL-10 A-592C polymorphism between patients with and without coronary artery lesions. The IL-10-592*A allele may be involved in the development of KD in Taiwanese children

The role of cytokine gene polymorphisms in the pathogenesis of abdominal aortic aneurysms: A case-control study

AbstractBackground: Cytokines are the primary mediators of inflammation and also influence matrix metalloproteinase expression, both of which are important in development of abdominal aortic aneurysm (AAA). A significant, but as yet unknown, familial factor contributes to the pathogenesis of AAA. Many cytokine genes contain polymorphic sites, some of which affect cytokine production in vitro. Cytokine gene polymorphisms may therefore influence the pathogenesis of AAA. The purpose of this study was to determine whether there is any association between cytokine gene polymorphisms and AAA. Methods and Results: This case-control study comprised 100 patients with AAA and 100 age-matched and sex-matched control subjects. For each case and control subject in the study, genotypes at the following cytokine gene polymorphic loci were determined: interleukin (IL)-1β +3953, IL-6 −174, IL-10 −1082, IL-10 −592, and tumor necrosis factors-α −308. Allele and genotype frequencies were compared between AAA and control groups, and odds ratios (OR) were calculated for the presence of AAA with each allele at each locus examined as risk factors. The IL-10 −1082 A allele was significantly more common in the AAA group than the control group (P =.03). The OR for the IL-10 −1082 A allele as a risk factor for AAA was 1.8 (95% confidence interval, 0.9-3.6). Discussion: These associations suggest a significant role for IL-10 in the pathogenesis of AAA. This association of AAA with the IL-10 −1082 A allele is also biologically plausible; the IL-10 −1082 A allele is associated with low IL-10 secretion, and it may be that AAA develops in patients who are unable to mount the same anti-inflammatory response as those who do not have AAA. (J Vasc Surg 2003;37:999-1005.

Interleukin-10 Promoter Polymorphism is Associated with the Predisposition to the Development of IgA Nephropathy and Focal Segmental Glomerulosclerosis in Korea

The roles of interleukin-10 (IL-10) have been emphasized in several models of glomerulonephritis (GN). Three biallelic polymorphisms within the IL-10 promoter region, at positions -1,082, -819, and -592 from the transcription initiation site, were shown to affect the level of IL-10 production. To investigate the effect of IL-10 promoter polymorphisms on the predisposition to development of GN in Korea, IL-10 promoter polymorphisms were assayed by polymerase chain reaction followed by restriction fragment length polymorphism in 108 patients with IgA nephropathy (IgAN), 49 focal segmental glomerulosclerosis (FSGS), and 100 healthy controls. In comparison with the control, the frequency of -1,082*G alleles were lower in IgAN and the frequencies of -592*C and -819*C were lower in FSGS, respectively. As for the haplotype, GCC haplotype was less frequent among IgAN than the control and ATA haplotype was more frequent among FSGS than the control (p<0.05). The frequency of intermediate producer genotypes (GCC/ACC and GCC/ATA) were lower among IgAN or FSGS than the control. Our findings suggested that IL-10 promoter polymorphism predisposed to the development of IgAN and FSGS in Korean patients

Association of genetic polymorphisms in the interleukin-10 promoter with risk of prostate cancer in Chinese

<p>Abstract</p> <p>Background</p> <p>Recent studies identified an increased risk of prostate cancer (PCa) in Caucasian men harboring polymorphisms of genes involved in innate immunity and inflammation. This study was designed to assess whether single nucleotide polymorphisms in the IL-10 promoter play a role in predisposing individuals to PCa in a Chinese population.</p> <p>Methods</p> <p>We genotyped three SNPs of the <it>IL-10 </it>promoter (-1082A/G, -819T/C and -592A/C) using polymerase chain reaction-restriction fragment length polymorphism analysis in 262 subjects with PCa and 270 age-matched healthy controls. Odds ratio and 95% confidence interval were determined by logistic regression for the associations between IL-10 genotypes and haplotypes with the risk of PCa and advanced PCa grade.</p> <p>Results</p> <p>No significant differences in allele frequency or genotype distribution were observed for any of the <it>IL-10 </it>SNPs between PCa patients and control subjects. Significantly higher frequencies of -1082G, -819C and -592C allele and GCC haplotype were observed, however, in early stage patients in comparison to advanced PCa patients (for -1082 G, 13.9% vs 6.1%, OR = 2.48, <it>P </it>= 0.005; for -819 C 40.3% vs 30.8%, OR = 1.51, <it>P </it>= 0.043; for -512C, 40.3% vs 30.8%, OR = 1.51, <it>P </it>= 0.043; and for haplotype GCC 11.1%vs 5.1%, OR = 2.66, P = 0.008, respectively).</p> <p>Conclusions</p> <p>Our results identify that <it>IL-10 </it>promoter polymorphisms might not be a risk factor for PCa in Chinese cohorts, but rather incidence of polymorphisms associates with PCa grade, suggesting that IL-10 expression may impact PCa progression.</p

Role of host genetics in fibrosis

Fibrosis can occur in tissues in response to a variety of stimuli. Following tissue injury, cells undergo transformation or activation from a quiescent to an activated state resulting in tissue remodelling. The fibrogenic process creates a tissue environment that allows inflammatory and matrix-producing cells to invade and proliferate. While this process is important for normal wound healing, chronicity can lead to impaired tissue structure and function