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author:("niewalda, TB")
3.  Association of the PTPN22 R620W polymorphism with increased risk for SLE in the genetically homogeneous population of Crete 
Lupus  2011;20(5):501-506.
Autoimmune diseases affect approximately 5% of the population, but much work remains to define the genetic risk factors and pathogenic mechanisms underlying these conditions. There is accumulating evidence that common genetic factors might predispose to multiple autoimmune disorders. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are complex autoimmune disorders with multiple susceptibility genes. The functional R620W (C1858T) polymorphism of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, a member of the PTPs that negatively regulate T-cell activation, has been recently associated with susceptibility to various autoimmune diseases. The aim of this study was to assess whether the C1858T polymorphism of PTPN22 also confers increased risk for SLE and RA in the genetically homogeneous population of Crete. It was found that the minor T allele of the PTPN22 C1858T SNP was more common in SLE patients than in control individuals (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.11 to 3.9, p = 0.017). No significant difference was observed in the frequency of this allele when RA patients were compared with controls (OR = 1.14, 95% CI = 0.65 to 1.9, p = 0.64). Although the PTPN22 1858T allele is found at decreased frequency in Southern Europe, including Crete, an association was found between this allele and SLE in the population studied.
PMCID: PMC3312778  PMID: 21543514
polymorphism; PTPN22 gene; rheumatoid arthritis; systemic lupus erythematosus
4.  Age- and gender-specific modulation of serum osteopontin and interferon-α by osteopontin genotype in systemic lupus erythematosus 
Genes and immunity  2009;10(5):487-494.
Osteopontin (OPN) is a multifunctional cytokine involved in long bone remodeling and immune system signaling. Additionally, OPN is critical for interferon-α (IFN-α) production in murine plasmacytoid dendritic cells. We have previously shown that IFN-α is a heritable risk factor for systemic lupus erythematosus (SLE). Genetic variants of OPN have been associated with SLE susceptibility, and one study suggests that this association is particular to men. In this study, the 3′ UTR SLE-risk variant of OPN (rs9138C) was associated with higher serum OPN and IFN-α in men (P = 0.0062 and P = 0.0087, respectively). In women, the association between rs9138 C and higher serum OPN and IFN-α was restricted to younger subjects, and risk allele carriers showed a strong age-related genetic effect of rs9138 genotype on both serum OPN and IFN-α (P<0.0001). In African-American subjects, the 5′ region single nucleotide polymorphisms, rs11730582 and rs28357094, were associated with anti-RNP antibodies (odds ratio (OR) = 2.9, P = 0.0038 and OR = 3.9, P = 0.021, respectively). Thus, we demonstrate two distinct genetic influences of OPN on serum protein traits in SLE patients, which correspond to previously reported SLE-risk variants. This study provides a biologic relevance for OPN variants at the protein level, and suggests an influence of this gene on the IFN-α pathway in SLE.
PMCID: PMC2762275  PMID: 19339987
systemic lupus erythematosus; interferon-α; osteopontin; age; gender; autoantibodies
5.  High serum IFN-α activity is a heritable risk factor for systemic lupus erythematosus 
Genes and immunity  2007;8(6):492-502.
Interferon α (IFN-α) levels are elevated in many patients with systemic lupus erythematosus (SLE); however it is not known whether high serum IFN-α activity is a cause or a result of the disease. We studied 266 SLE patients and 405 of their healthy relatives, and frequently found high serum IFN-α activity in both patients and healthy relatives as compared to healthy unrelated individuals. High IFN-α activity was clustered in specific families in both SLE patients and their healthy first-degree relatives, suggesting a heritable trait. Heritability was also supported by quantitative familial correlation of IFN-α activity, concordance in affected sib pairs and frequent transmission of the high IFN-α activity trait from parents to offspring. Autoantibodies to RNA-binding proteins and double-stranded DNA were associated with high IFN-α activity in SLE patients; however these autoantibodies were very uncommon in healthy family members and did not explain the observed familial correlations. The frequency of high IFN-α activity was similar across all studied ethnic backgrounds. These data suggest that high serum IFN-α activity is a complex heritable trait, which plays a primary role in SLE pathogenesis.
PMCID: PMC2702174  PMID: 17581626
interferon α; systemic lupus erythematosus; genetics; epidemiology; autoantibodies

Results 1-5 (5)