Andrzej Obojski

Association of PTPN22 single nucleotide polymorphism with rheumatoid arthritis but not with allergic asthma.

PTPN22 gene encodes a lymphoid tyrosine phosphatase (LYP), an important negative regulator of T-cell responses. The 1858C>T (Arg620Trp) single nucleotide polymorphism (rs2476601) was found associated with autoimmune diseases, including rheumatoid arthritis (RA). Allergic diseases are similar to autoimmune diseases, by an exaggerated immune response to an antigen (allergen in this case) normally not invoking such response in healthy individuals. We investigated whether polymorphism 1858C>T in PTPN22 gene is associated with susceptibility to allergic asthma and RA in a Polish population. PTPN22 was genotyped in 173 patients with RA, in 198 patients with allergic asthma, and in 543 controls using PCR-RFLP. The patients with RA differed from healthy controls in frequencies of PTPN22 1858C>T alleles (P=0.0004; odds ratio (OR), 1.8; 95% CI, 1.33–2.55) and genotypes (P=0.0009). Strong associations of 1858T allele with RA limited to joints (0.21 vs 0.12, P=0.0002; OR, 2.1; 95% CI, 1.44–3.00), with erosive disease (0.20 vs 0.12, P=0.0003; OR, 1.92; 95% CI, 1.34–2.71), with a lack of rheumatoid factor (RF; 0.23 vs 0.12, P=0.0008; OR, 2.29; 95% CI, 1.44–3.63), and weak association with the presence of RF (0.17 vs 0.12, P=0.02; OR, 1.6; 95% CI, 1.10–2.40) in comparison with healthy controls were observed. Very strong association of 1858T allele (P<0.0001; OR, 2.72; 95% CI, 1.9–3.9) and T phenotype (P<0001; OR, 3.2; 95% CI, 2.1–4.9) with antibodies to cyclic citrullinated peptide (CCP) was found. When patients with allergic asthma were typed for PTPN22 1858C>T polymorphism, no difference with control was found. Subdivision of patients into those with mild, moderate, or severe asthma did not reveal any associations. In conclusion, we confirmed associations between several clinical manifestations of RA and PTPN22 1858T allele. However, no association with 1858C>T polymorphism was found for susceptibility to allergic asthma or for severity of the disease.

Distribution of CTLA-4 polymorphisms in allergic asthma.

Background: The CTLA-4 molecule is an important negative regulator of T cell activation. It is encoded on chromosome 2q33 and found to be associated with several allergic phenotypes including asthma. However, the association of CTLA-4 gene polymorphisms with allergic asthma is still controversial and therefore was the subject of this study. Methods: By PCR-RFLP, the distribution of three single nucleotide polymorphisms (SNPs), –1147 C/T, –318 C/T, and +49 A/G, was examined in 219 Polish Caucasoid patients diagnosed with allergic asthma and in 102 ethnically matched healthy control individuals. (AT)n microsatellite polymorphism was also tested in the same individuals. Results:No statistically significant differences in SNPs or microsatellite allele, genotype or haplotype frequencies between patients and controls were found. Conclusion:CTLA-4 polymorphisms do not seem to be a risk factor for allergic asthma in Poles.

Impact of Birth Weight and Smoking on Lung Function in Patients with Asthma, COPD, and Healthy Volunteers

BACKGROUND Birth weight (BW) is an important factor for determining the development of the respiratory system. The majority of research analyzed the impact of BW on lung function in youth. BW influence and smoking on lung function in adults with asthma and COPD is an interesting issue. OBJECTIVES The aim of the study was to investigate relationships between BW, smoking, and lung function in adult healthy individuals and diagnosed with asthma or COPD. MATERIAL AND METHODS Four hundred seventy-nine subjects were divided into 5 groups: 123 healthy non-smokers, 180 healthy smokers, 72 non-smoking asthmatics, 57 smoking asthmatics, and 47 COPD patients. Relationships between 4 BW quartiles and lung function was analyzed with respect to smoking. RESULTS Impact analyzes of BW, smoking, and asthma on FVC% revealed that asthma is the only significant differentiating factor in this spirometric parameter (p < 0.01). FEV1% was significantly influenced by asthma and BW, and FEV1/ FVC% was exclusively influenced by asthma. Spirometric parameters increased proportionally to particular BW quartiles in healthy non-smokers group; however optimal BW quartile predicting increase of parameters was 2751-3250 g. In asthma, BW quartile predicting the increase of spirometric parameters was 3251-3750 g, but BW quartile predicting decrease of FEV1/FVC% was 2751-3250 g. The comparison of results between COPD group and results from other 4 groups showed that values of all parameters in patients with COPD did not change proportionally to all quartiles of BW. In terms of FEV1/FVC%, the proportional increase of parameter in BW quartile 2751-3250 g was observed. CONCLUSIONS BW, as independent factor influences on spirometric parameters of healthy individuals, patients with asthma, COPD in a differentiated manner depending on quartile of BW rather than on simple linear increase of BW, regardless of smoking.