The association of angiotensin-converting enzyme gene insertion/deletion polymorphism with bronchial asthma.

Bronchial asthma (BA) is among the most prevalent chronic inflammatory disorders of the lung airways, and it has become clear that a mixture of genetic predisposition and environmental factors plays a critical role in its pathogenesis. The aim of presented review is to analyze the published data on the possible role of ACE gene polymorphism in BA development. The article is based on available literature found in Pubmed, Elsevier, Scopus, and Google scholar databases. We have found that ACE I/D polymorphism may contribute to an important molecular mechanisms of BA development (specially D/D genotype), and may become a useful tool in risk assessment and in designing effective treatment approaches. The difference in the literature on the role of ACE alleles and genotypes can be explained by minor influence of the investigated genetic component and contributions of other genetic variations, as well as other environmental factors, considering multifactorial causes of BA.

The effect of immunoregulatory bacteria on the transcriptional activity of Foxp3 and RORyt genes in the gut-associated lymphoid tissue with Salmonella-induced inflammation in the presence of vancomycin and Bacteroides fragilis.

BACKGROUND AND OBJECTIVES: Intestinal microbiota is involved in the development and maintenance of immune homeostasis. This study was conducted to investigate the levels of key immunoregulatory bacteria in the intestinal wall-associated microflora and its effect on the transcriptional activity of the Foxp3 and RORyt genes in the gut-associated lymphoid tissue (GALT) of rats with Salmonella-induced inflammation, both untreated and treated with vancomycin and Bacteroides fragilis. MATERIALS AND METHODS: To determine the levels of immunoregulatory bacteria in GALT of rats Q-PCR was used to identify them by species-specific 16S rDNA genes. Transcriptional activity of Foxp3 and RORyt genes was determined using Q-PCR with reverse transcription. RESULTS: In animals treated with both vancomycin and Salmonella, the levels of segmented filamentous bacteria (SFB) increased while Akkermansia muciniphila and Faecalibacterium prausnitzii decreased. In rats that received pretreatment with vancomycin and then were infected with S. Enteritidis and S. Typhimurium, the levels of SFB increased, and the number of Bacteroides-Prevotela group, A. muciniphila, Clostridium spp. clusters XIV, IV, and F. prausnitzii significantly decreased, decreasing Foxp3 and increasing Rorγt mRNA expression. Administration of B. fragilis to animals treated with S. Enteritidis or S. Typhimurium and pre-treated with vancomycin caused a decrease in SFB and Rorγt mRNA levels and conversely, increased the numbers of the Bacteroides-Prevotela group, Clostridium spp. clusters XIV, IV, A. muciniphila, F. prausnitzii and Foxp3 gene expression in GALT. CONCLUSION: Our results suggest that the commensal microorganism B. fragilis may provide a protective role against the development of experimental colitis, which has to be taken into consideration for further clarification of the effective therapeutic strategy of inflammatory bowel diseases, irritable bowel syndrome and necrotising colitis.

The effect of folate-related SNPs on clinicopathological features, response to neoadjuvant treatment and survival in pre- and postmenopausal breast cancer patients.

This study aimed to investigate the relationship of ten single nucleotide polymorphisms (SNPs) in the MTHFR, MTR, MTRR, DHFR, MTHFD1, TS, RFC1 and DNMT3b genes with cancer survival, therapeutic response to neoadjuvant chemotherapy and clinicopathological characteristics in 300 pre- and postmenopausal breast cancer patients of a Russian Western Siberian population. We found that the MTHFR 677CT genotype as well as combination of MTHFR 677CT and 677TT genotype was related to tumor size and estrogen-positive status in postmenopausal group. The RFC1 80А allele was associated with an increased risk of lymph node metastases among postmenopausal women. The MTHFR 677TT genotype was significantly correlated with a better progression-free survival in premenopausal patients. In contrast, a worse outcome was observed in this group patient with MTHFD1 1958AA genotype. In the multivariate analysis, the MTHFD1 1958AA genotype was identified as an independent prognostic factor for premenopausal breast cancer survival. Our findings provide evidence for associations of breast cancer survival with folate-related SNPs in a population of Western Siberian region of Russia and the MTHFD1 (1958G>A) may have additional prognostic value especially among premenopausal patients.