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Plasminogen activator inhibitor-1 (PAI-1) is a glycoprotein which has a role in tissue remodelling after inflammatory processes. The objective is to investigate the frequency of PAI-1 gene polymorphism (4G/5G) in patients with a lung ventilation dysfunction in asthma and allergic rhinitis. Genomic DNA was isolated and genotypes of polymorphism of PAI-1 4G/5G and ABO were determined using the methods of RT-PCR and PCR-SSP. Study group includes 145 adult patients diagnosed with chronic asthma, with all clinically relevant parameters and the laboratory markers of pO 2 , IgE and eosinophils in sputum and nasal swab. In the processing of data, appropriate statistical tests (Kolmogorov-Smirnov test, median, interquartile ranges, χ 2 and Mann-Whitney U tests) were used. Patients with symptoms of allergic rhinitis were significantly younger and had an almost four time higher levels of IgE (P = 0.001), higher pO 2 (P = 0.002) and PEF (P = 0.036), compared to those who do not have these symptoms. Genotype PAI 4G/4G is significantly more common in patients with allergic rhinitis (28.1% vs. 16.1%; P = 0.017) compared to the genotype 5G/5G. Carriers of the genotype 4G/5G also have a borderline statistical significance. There were no statistically significant difference in the incidence of allergic rhinitis in the carriers of any ABO genotypes. The frequency of PAI genotype 4G/4G is significantly more common in patients with allergic rhinitis. The results suggest that the carriers of at least one 4G allele are at a higher risk for developing symptoms of allergic rhinitis in asthma.

The aim of this study was to test the hypothesis that glutathione- S-transferase (GST) genotypes were associated with COPD. GSTP1, GSTM1 and GSTT1 genotypes were determined by DNA methods and GST activity spectrophotometrically in older male Caucasian Croats (non- -smokers, ex-smokers, and smokers) with stable COPD (n = 30) and sex/age matched controls (n = 60). The distribution of GSTP1 genotypes and alleles in controls vs. COPD showed a statistical difference (p < 0.05). The odds ratio of CC/CT+TT (wild type GSTP1 exon 6 vs. joint heterozygous and mutant homozygous GSTP1 exon 6) was 10.000 and statistically different (p = 0.002). In this study, the GSTP1 mutant genotype of exon 5 (GG), as well as GSTP1 mutant and heterozygous genotypes of exon 6 (TT and CT), were suggested to be genetic contributors to COPD susceptibility. Null GSTM1, null GSTT1 and joint GSTM1/GSTT1 null genotypes were not disease associated. Serum GST was not associated with GST genotypes and COPD or smoking history in our study subjects. Conclusions drawn from the study should be further supported and clarified by studies with larger sample sizes.

The impact of glutathione S-transferases (GSTs) detoxification pathway on complex pathogenesis and heterogeneity of clinical findings in multiple sclerosis (MS), particularly the exact correlation between indicators of clinical severity and different GST genotypes, has not yet been fully elucidated. The aim of the study was to assess the relationship between disability level in multiple sclerosis (estimated by Kurtzke Expanded Disability Status Scale), disease progression (estimated by Multiple Sclerosis Severity Score), the level of brain atrophy and lesion load (determined by MRI) and detoxification status (analyzing glutathione S-transferase P1, GSTP1, genotype profile), in a group of 58 MS patients and 68 age/gendermatched controls. The results present the first evidence on significantly higher frequency of GSTP1 C341T polymorphism (C-T transition) in healthy subjects compared to MS patients, suggesting it may act as a moderating factor in developing MS clinical phenotype. Gender-dependent distribution of the C341T polymorphism was found in both MS patients and controls, with higher frequency of C-T transition in females. In addition, preliminary data showed higher proportion of male MS patients with higher median MSSS scores, as well as lower brain atrophy level and lesion load in MS patients carrying the C341T mutation. Observed gender difference in distribution of the C341T polymorphism in MS patients, as well as in disease progression, suggests that GSTP1 detoxification pathway occurs in a gender-dependent manner and could therefore add to clinical severity in male MS patients.