Previous studies of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in sarcoidosis have revealed both ethnic heterogeneity of I/D frequencies and controversy surrounding the association between the polymorphism and severity of disease. The objective of this study was, therefore, to clarify the role of the ACE I/D polymorphism in (1) disease susceptibility, (2) pulmonary disease severity (with particular reference to pulmonary fibrosis), and (3) pulmonary disease progression, in two distinct European sarcoidosis populations. Standard chest radiographic staging was performed on 118 UK and 56 Czech white patients with sarcoidosis at 2 yr from presentation. Pulmonary function data were analyzed, and patients were then categorized according to disease severity. A PCR-SSP assay was used to determine the ACE I/D genotype of each patient studied. The I/D allele frequencies from these patients were compared with frequencies from ethnically matched UK (n = 386) and Czech (n = 179) control subjects using a chi-square contingency table. No significant differences were seen in the distribution of the ACE I/D genotypes, allele frequencies or phenotype frequencies. Furthermore, no association was found between the ACE I/D polymorphism and pulmonary disease severity, fibrosis, and progression. We conclude that the ACE I/D polymorphism has no role in sarcoidosis susceptibility in European whites and that it is not a regulatory variant in this disease.

Associations of the genetic polymorphisms in the promoter region and the signal peptide sequence of the transforming growth factor-beta (TGF-beta1) gene with proliferative diabetic retinopathy (PDR) in patients with non-insulin-dependent diabetes mellitus (NIDDM) were studied. A total of 245 Caucasian subjects comprised the two groups: NIDDM patients with PDR (n = 73) and NIDDM patients without PDR (n = 172). Allele frequencies of common TGF-beta1 polymorphisms (at positions -988C/A, -800G/A, -509C/T, +869T/C (L10P), and +915G/C (R25P)) were determined by PCR-based methodology. All polymorphisms were in strong linkage disequilibrium (P < 10(-2)). Significantly higher frequencies of both the L allele and the R allele of the signal sequence polymorphisms in PDR subjects were found (after a correction for multiple comparisons, P(corr) < 10(-2) and P(corr) < 10(-4), respectively). Calculated odds ratios (ORs) for the LL and RR genotypes were 2.89 (95% confidence interval (CI), 1.6-5.1) and 19.73 (95% CI, 2.6-146.8), respectively. No significant differences between groups were found for the -800G/A and -509C/T polymorphisms. The -988A allele was not represented in our sample. Multiple logistic regression identified age, diabetes duration, and R25P polymorphism as significant predictors (P = 0.002, P = 0.000003, and P = 0.007, respectively). The frequencies of genotype combinations of the -800G/A, -509C/T, L10P, and R25P TGF-beta(1) polymorphisms were significantly different between the PDR and non-PDR groups (chi(2) = 37.83, df = 20, P < 10(-2)). The frequency of haplotype consisting of majority alleles was found significantly associated with PDR (P < 0.03). The presented data indicate that the R25P polymorphisms in the TGF-beta1 gene could be regarded as a strong genetic risk factor for PDR.

The aims of this retrospective computed tomography (CT) study were to determine the occurrence of severe root resorption involving the pulpal canal of adjacent permanent teeth associated with ectopically erupting canines, and to verify the existence of related factors. The sample consisted of 255 consecutive patients (159 females and 96 males, mean age 18.4 and 16.8 years, respectively). Three hundred and thirty-four ectopic maxillary canines and adjacent teeth were analysed using CT images. Statistical significance was evaluated with chi-square and Fisher's exact tests. The results showed that severe root resorption of adjacent permanent teeth occurred in 17.7 per cent of ectopic canines and was equally common in females and males. Severe root resorption affected 12.6 per cent of the lateral incisors, 4.8 per cent of the first premolars, and 2.1 per cent of the central incisors. No relationship was found between the type or side of ectopic eruption, inclination of the longitudinal axis of the ectopic canine and the occurrence of severe root resorption. A significant relationship was found between a bucco-lingual position of the ectopic canine and root resorption (P < 0.05). Root resorption mainly occurred in the apical third (57.6 per cent) and apical and middle thirds (27.1 per cent). A significant relationship existed between the occurrence of root resorption and complete loss of space for the erupting canine (P < 0.05). No association was found between alignment of the upper permanent incisor and root resorption. A widened dental follicle occurred in 15 per cent of ectopic canines but did not cause root resorption of the adjacent permanent teeth. Since root resorption is asymptomatic, early detection by radiographic examination is essential for correct diagnosis and treatment.

The study aimed to examine an association of three different single nucleotide polymorphisms (SNPs) of the IL-18 gene (-607 C/A, -137 G/C and -133 C/G) on chromosome 11q22 with allergic rhinitis (AR). Genotyping for the SNPs was performed using 539 patients with AR and 312 healthy control volunteers. Positivity to the skin prick test for the fungus Alternaria sp. in patients with AR, and IgE levels according to particular genotypes of selected SNPs, were also determined. There were no significant differences in the distribution of single IL-18 alleles or genotypes between controls and AR patients. However, frequencies of combined IL-18 genotypes arising from combinations of the three common polymorphisms (-607, -137 and -133) were significantly different between both groups (P = 0.009, P corr < 0.05, OR = 5.35, 95% CI: 1.9-15.2). There was a marginally significant association of the IL-18-607 variant with IgE levels (P = 0.05) in patients, but not in the case of the other SNPs. Patients allergic to Alternaria, but not those allergic to other antigens, showed a significant association with the IL-18-607 polymorphism (P = 0.0037, P corr < 0.05). Results suggest that IL-18 gene variants may be one of the factors participating in the pathogenesis of AR or its intermediary phenotypes.