Beata Loniewska

ADA*2 Allele of the Adenosine Deaminase Gene May Protect against Coronary Artery Disease

Background/Aims: The common G22A polymorphism in the adenosine deaminase (ADA) gene leads to substitution Asp8Asn. The lower activity of the enzyme encoded by A22 (ADA*2) allele may increase tissue concentrations of adenosine, a potent cardioprotective agent. In a case-control study, we investigated the association between ADA polymorphism and coronary artery disease (CAD). Methods: A hundred and seventy-one CAD patients from the north-western part of Poland and 200 consecutive newborns from the same population were genotyped by PCR-RFLP. Results: Twenty-five ADA*1/*2 heterozygotes (12.5%) and 2 ADA*2/*2 homozygotes (1%) were found in the control group, while only 10 *1/*2 heterozygotes (5.9%) and no *2/*2 homozygotes were found in the CAD group. Frequencies of ADA*2 carriers (5.9% vs. 13.5%, p = 0.015) and ADA*2 allele (2.9% vs. 7.3%, p = 0.0083) were lower in CAD patients than in controls. Among CAD patients, a significantly lower proportion of *2 allele carriers was treated with diuretics and ACE inhibitors when compared to *1/*1 wild-type homozygotes. Conclusion: ADA*2 allele may decrease genetic susceptibility to CAD. ADA should be added to the list of candidate genes modifying the risk of cardiovascular diseases.

The distribution of human endogenous retrovirus K-113 in health and autoimmune diseases in Poland

OBJECTIVE During the evolution of the human genome, a number of retroviral integrations have occurred creating a group of human endogenous retroviruses (HERVs). As of now several studies have pointed to the association of HERVs with certain autoimmune diseases such as RA, SLE, multiple sclerosis (MS) and SS as well as various neoplasms. In this study, we investigated the prevalence of HERV-K113 in patients with RA, SLE and in healthy subjects in the Polish population. METHODS Genomic DNA samples from 155 RA patients, 139 SLE patients and 261 newborns (as controls) were tested for the presence of the HERV-K113 allele using PCR. Each individuals DNA was genotyped for null, homozygous or heterozygous insertion of HERV-K113. RESULTS Our data revealed statistically significant differences in the insertion frequencies of HERV-K113 between the groups of RA and SLE patients vs healthy controls (provirus DNA was found in 14.19, 15.11 and 8.05% of individuals, respectively). No homozygous individuals for the K113 allele were found in each of the groups. There was no evidence for HERV-K113 association with clinical features in either group. CONCLUSION Our study-the first such performed for the Polish population-provides a consistent observation with previous reports on the genetic association of HERV-K113 integrations in autoimmune disorders. Here, we found that the prevalence of insertionally polymorphic HERV-K113 was significantly increased in Polish patients with SLE and RA.

Association of C34T AMPD1 gene polymorphism with features of metabolic syndrome in patients with coronary artery disease or heart failure.

Objective. The common C34T polymorphism in the AMP deaminase‐1 (AMPD1) gene results in an inactive enzyme in homozygotes for the mutated T allele. Some studies have shown an association of T allele with longer survival in heart failure (HF) and/or coronary artery disease (CAD). The aim of this study was to assess genotype–phenotype correlations in such patients, with emphasis on components of the metabolic syndrome. Methods. Ninety‐seven patients with CAD without HF (CAD+ HF–) and 104 with HF (HF+) were genotyped by PCR‐RFLP. The genetic control group comprised 200 newborns. Results. No significant differences were found in the frequency of AMPD1 genotypes between the groups. In the CAD+ HF– group, the carriers of T allele compared to CC homozygotes had significantly lower values of waist circumference (89.5±8.5 versus 97.7±11.2 cm; p = 0.00029), waist/hip ratio (p = 0.0059) and BMI (p = 0.045). There was no diabetes or fasting glycaemia ⩾126 mg/dL in T carriers, while these features were present in 25 % of CC homozygotes (p = 0.0024). In the HF+ group, a tendency towards a lower prevalence of diabetes (20 % versus 41 %; p = 0.068) and significantly lower systolic blood pressure (p = 0.048) were observed in T allele carriers. Conclusions. C34T AMPD1 polymorphism may be associated with reduced frequency of obesity in CAD patients and of hyperglycaemia and diabetes in both CAD and HF patients. Morphometric parameters associated with adipose tissue distribution and parameters of glucose metabolism should be analysed as potential confounders in further studies on the role of polymorphisms of AMPD1 and other genes associated with AMP and adenosine metabolism in cardiovascular disease.

Frequency of common CYP3A5 gene variants in healthy Polish newborn infants

Cytochrome P450 monooxygenases catalyze the metabolism of approximately 40-60% of widely used drugs with a A6986G CYP3A5 polymorphism determining expresser (A6986, *1) and reduced- expresser (*3) variants with modified drug metabolism activity. In this report, the allele frequency of CYP3A5 *1 and *3 (A6986 or G6986, respectively) was analyzed by the PCR-RFLP technique in a cohort of 200 Polish newborns from the West Pomeranian region. Of the studied group, 1% (n = 2/200) proved homozygous for the CYP3A5*1 allele, 89% (n = 178/200) for the *3 allele, and 10% (n = 20/200) were heterozygous for *1/*3. Similar frequencies were found in other Caucasian European populations. This study provides basic genetic data related to the metabolism of drugs, with a narrow therapeutic window in a Polish population.

From clinical uncertainties to precision medicine: the emerging role of the gut barrier and microbiome in small bowel functional diseases

ABSTRACT Introduction: Over the last decade, remarkable progress has been made in the understanding of disease pathophysiology. Many new theories expound on the importance of emerging factors such as microbiome influences, genomics/omics, stem cells, innate intestinal immunity or mucosal barrier complexities. This has introduced a further dimension of uncertainty into clinical decision-making, but equally, may shed some light on less well-understood and difficult to manage conditions. Areas covered: Comprehensive review of the literature on gut barrier and microbiome relevant to small bowel pathology. A PubMed/Medline search from 1990 to April 2017 was undertaken and papers from this range were included. Expert commentary: The scenario of clinical uncertainty is well-illustrated by functional gastrointestinal disorders (FGIDs). The movement towards achieving a better understanding of FGIDs is expressed in the Rome IV guidelines. Novel diagnostic and therapeutic protocols focused on the GB and SB microbiome can facilitate diagnosis, management and improve our understanding of the underlying pathological mechanisms in FGIDs.