Emergency medicine pharmacotherapy compromises accuracy of plasma creatinine determination by enzyme-based methods: real-world clinical evidence and implications for clinical practice.

Background: Assessment of kidney function in emergency settings is essential across all medical subspecialties. Daily assessment of patient creatinine results from emergency medical services showed that some deviated from expected values, implying drug-related interference. Methods: Real-time clinical evaluation of an enzyme method (Roche CREP2) in comparison with the Jaffé gen. 2 method (Roche CREJ2) was performed. During the period of December 2022 and January 2023, we analyzed 8,498 patient samples, where 5,524 were heavily medicated STAT patient specimens, 500 were pediatric specimens, and 2,474 were from a distant general population in a different region using the same methods. Results: In 109 out of 5,524 hospital specimens (1.97%, p < 0.001), the CREP2 value was apparently (25% or more) lower than CREJ2. Suspect interfering medication was found in a sample of 43 out of 46 reviewed patients where medication data were available. This phenomenon was not observed in the general population. Conclusion: In a polymedicated urgent care hospital population, a creatinine enzyme method produces unreliable results, apparently due to multiple drug-related interferences.

Haplotype analysis of the interleukin-18 gene in Czech patients with allergic disorders.

The interleukin-18 (IL-18) gene on chromosome 11q22 has been suggested as a susceptibility factor for allergies. To test for a possible role of IL-18 polymorphisms in Czech population, case-control study including 958 subjects (633 allergic patients and 325 healthy controls) was performed. An allele-specific polymerase chain reaction was used to analyze variants at positions -607 C/A (rs1946518) and -137 G/C (rs187238) in the promoter region together with the polymerase chain reaction-restriction fragment length polymorphism method for the detection of polymorphism at position -140 C/G (previously -133 C/G, rs360721) in intron 1 of the IL-18 gene. The -1297 C/T (rs360719) polymorphism was genotyped by real-time-polymerase chain reaction, using a predevelopment TaqMan allele discrimination assay. There were no significant differences in distribution of alleles or genotypes in any of four single nucleotide polymorphisms in the IL-18 gene between controls and patients. However, subsequent analysis revealed a significant difference in haplotype frequencies between the allergic patients and healthy subjects (p < 0.01). Haplotype formed by -1297 C/-607 A/-137 C/-140 C alleles occurred significantly more frequently in patients than controls (0.0433 vs 0.0129; p < 0.0003; p(corr)< 0.01, OR = 3.37; 95% CI = 1.59-7.14). In contrast, there was no relationship among the IL-18 variants and total serum IgE level. Our results indicate that promoter polymorphisms in the IL-18 gene act in interaction and could play a role in allergic disorders.

Polymorphisms of the CD14 gene and atopic phenotypes in Czech patients with IgE-mediated allergy.

IgE-mediated allergy is a common chronic disorder resulting from interactions between genetic and environmental factors. The gene encoding CD14 is a positional candidate gene for allergic diseases as it is localised on chromosome 5q31.1, a region linked to asthma and bronchial hyperresponsiveness. We investigated the relationship among atopic phenotypes and six polymorphisms in the CD14 gene. Polymerase chain reaction with RFLP analyses was used to determine the CD14 genotypes in subjects with IgE-mediated allergic diseases (n=282) and random controls (n=187). No significant differences in allele or genotype frequencies for individual polymorphisms between patients and controls were found. However, when atopic patients were subdivided into subjects with positive and with negative skin prick tests for separate antigens, T allele of the 1341G/T polymorphism was significantly associated with positive reactivity to mites (P=0.007) and moulds (P=0.041). Similarly, the C allele frequency of the -159C/T variant was increased in patients with positive skin prick tests for mites (P=0.046) and moulds (P=0.056). In haplotype analysis, the common -1619A/-1359G/-550C/-159C/+1188G/+1341T haplotype was associated with positive reaction to these antigens (P values: 0.0008-0.0035). Our study supports the idea that CD14 plays a role in IgE-mediated allergic diseases, and its gene polymorphisms can be important for manifestation of these disorders.

Polymorphisms in the +252(A/G) lymphotoxin-alpha and the -308(A/G) tumor necrosis factor-alpha genes and susceptibility to chronic periodontitis in a Czech population.

BACKGROUND: Periodontitis is an inflammatory disease that leads to irreversible attachment loss, bone destruction and eventually tooth loss. Tumor necrosis factor (TNF), a pluripotent proinflammatory cytokine that is able to induce tissue destruction and bone resorption, has been implicated in the pathogenesis of periodontal disease. METHODS: In this study, we investigated an association between chronic periodontitis and two previously described bi-allelic polymorphisms in the TNF locus: a G to A transition at position -308 in the 5'promoter region of the TNF-alpha gene and an NcoI restriction fragment length polymorphism (RFLP) in the first intron (position +252A/G) of the lymphotoxin alpha (LT-alpha) gene. Genomic DNA was obtained from 132 patients with chronic periodontitis together with 114 age- and gender-matched unrelated control subjects. RESULTS: The TNF-alpha (-308G/A) polymorphism itself showed no association with chronic periodontitis, whereas the frequency distribution of the LT-alpha (+252A/G) genotypes showed statistically significant differences between patients and the reference group. The proportion of individuals carrying the LT-alpha 1/1 genotype was significantly lower in the group of patients with chronic periodontitis (0.8%) than in the control group (8.8%) (P < 0.0094, Pcorr < 0.05). However, the significant differences in the frequencies of the combined genotypes (TNF-alpha and LT-alpha) between the control and the patient groups were found using a simulation by applying the Monte-Carlo method (P < 0.01). CONCLUSION: Our data suggest that combined genotypes composed of the TNF-alpha and LT-alpha gene polymorphisms may influence the susceptibility to chronic periodontitis. We also showed that, comparing the two genes, the 1/1 genotype of the NcoI polymorphism in the first intron of the LT-alpha gene is a more informative marker and it may be one of the protective genetic factors against chronic periodontitis in our population.

The role of the IKAP gene polymorphisms in atopic diseases in the middle European population.

Over ten genome-wide screens and many candidate genes studies were performed worldwide to elucidate genetic factors involved in the pathogenesis of bronchial asthma and other atopic diseases. Results from these studies were often discordant, which might have reflected complexity and heterogeneity of these multifactorial diseases. Among a variety of other loci, specific variants of the gene for IKAP (IKK complex-associated protein) were shown to be associated with bronchial asthma in children in a Japanese study. To test the possible role of SNPs in the coding region of the IKAP gene in atopic asthma or other atopic phenotypes in a highly homogenous Czech population, a case-control study including 373 patients and 309 healthy control subjects was performed. There were no significant differences in the genotype and allele distributions for any of five SNPs in the IKAP gene (T819C, G2295A, A2490G, T3214A and C3473T) between patients with atopic asthma or other atopic diseases and healthy controls. These results suggest that the polymorphisms in the coding region of the IKAP gene are unlikely to contribute to atopic disease risk in the Czech population.

Lack of association between atopic asthma and the tumor necrosis factor alpha-308 gene polymorphism in a Czech population.

Susceptibility to the development of asthma and other atopic diseases is known to be associated with genetic components. Several investigators have linked the tumor necrosis factor (TNF) genes and nearby markers located on chromosome 6p to atopy and asthma. A recent study has demonstrated that the TNF-alpha*2 allele of a polymorphism in the TNF-alpha gene promoter region (G-308 A) is associated with a higher risk for the development of atopy in Spanish patients. This study evaluates the possible role of two described bi-allelic polymorphisms in the TNF locus [a G to A transition at position-308 in the 5'-promoter region of the TNF-alpha gene and an NcoI restriction fragment length polymorphism (RFLP) in the first intron (+252A/G) of the LT-alpha(TNF-beta) gene] in atopic diseases in a Czech population. We investigated the distribution of these polymorphisms in a case-control study. The genotypes were determined in 151 patients with atopic asthma and 155 randomly sampled control subjects. The genotype frequencies for both polymorphisms were similar in cases and controls. No significant differences in allele frequencies were found between either of the patients groups and the reference subjects. Similarly, there were no associations of any of the examined variants of the TNF genes with total IgE, specific IgE or pulmonary function tests in patients with allergic diseases. We conclude that these polymorphisms of the TNF genes are unlikely to contribute to atopic disease risk in our population. Significant associations that have been reported in other studies may reflect the genetic heterogeneity of these complex diseases.