Association of 22 cytokine gene polymorphisms with rheumatoid arthritis in population of ethnic Macedonians.

To examine the possible role of 22 cytokine gene polymorphisms in host susceptibility to or protection against RA in Macedonians. In this study, 301 healthy unrelated individuals and 85 patients with RA were studied. Cytokine genotyping was performed by PCR with sequence-specific priming (PCR-SSP) (Heidelberg kit). Results showed susceptible association for four cytokine alleles, six cytokine genotypes, one haplotype, and four combinations of haplotypes, while protective associations were found for four cytokine alleles, three cytokine genotypes, three haplotypes, and only one combination of haplotypes. These results suggest that IL-4 -1098, IL-4 -590, IL-10 -1082, IL-10 -819, IL-2 -330, IL-6 -174, and TNF-alpha -238 cytokine gene polymorphisms might be significantly associated and affect host susceptibility and/or resistance to RA in Macedonians.

Association of cytokine gene polymorphisms with chronic obstructive pulmonary disease in Macedonians.

The aim of this study was to examine the association of 22 cytokine gene polymorphism in Macedonians with chronic obstructive pulmonary disease (COPD). The sample of the population comprised of 301 normal respondents and 62 patients with COPD. Cytokine genotyping was performed by polymerase chain reaction with sequence-specific priming (PCR-SSP). Positive (susceptible) association was found between patient with COPD and IL-1alpha -889/C allele; where as negative (protective) association among was found for the following alleles IL-1beta +3962/C; IL-12B -1188/A; IFNgamma +874/T; IL-2 -330/G; IL-4 -1098/G and IL-4-33/C. We found positive (susceptible) association between patients with COPD and following genotypes: IL4 -33/T:T; IFNgamma +874/A:A; IL-4 -1098/T:T ; IL-1alpha -889/C:C; IL-1beta +3962/C:T; IL-12B -1188/C:C; IL-4Ralpha +1902/G:G; IL-10 -1082/G:G; IL-2 -330/T:T; IL-4 -590/C:C; and IL-1alpha -889/C:T. Negative (protective) association between patients with COPD and following genotypes was found: IFNgamma +874/A:T; IL-4 -33/C:T; IL-4 -1098/G:T; IL-2 -330/G:T; IL-1beta +3962/C:T; IL-4 -590/C:T; IL-10 -1082/A:G; and IL-4 -33/C:C. Positive (susceptible) association between patients with COPD and following haplotypes was found: IL-4/TCT; IL-10/ATC; and IL-2/TG, and negative (protective) association was found between the patients with COPD and haplotypes for: IL-4/TTC; and IL-4/GCC. It could be concluded that several cytokine polymorphisms are positively (susceptible), or negatively (protective) associated with COPD in Macedonians.

CTLA-4 exon 1 polymorphism in patients with autoimmune blood disorders.

CTLA-4 is a CD28 homologue that plays an important role in negative regulation of T-cell responses. Its transient expression on the surface of activated T cells antagonizes the activating signals and terminates the T-cell response. An A to G polymorphism at position 49 of the CTLA-4 first exon has recently been associated with several autoimmune disorders. In the present study we have examined the prevalence of the A and G alleles of the CTLA-4 gene in 50 patients with autoimmune hemolytic anemia (AIHA), of which 20 had idiopathic AIHA and 30 had AIHA and chronic lymphocytic leukemia (CLL), and in 60 patients with immune thrombocytopenic purpura (ITP). Control subjects were 100 healthy individuals and 100 CLL patients without clinical evidence for an autoimmune disease. The G allele was present at a significantly higher frequency among the patients with AIHA (P = 0.003), whereas no difference was observed between patients with ITP and controls. The G allele frequency was highest among CLL patients who had developed AIHA. The obtained data indicate that the G allele of CTLA-4 predisposes to the development of AIHA, particularly among patients with CLL.