Alina Kanikowska

A novel approach to genome-wide association analysis identifies genetic associations with primary biliary cholangitis and primary sclerosing cholangitis in Polish patients

BackgroundPrimary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are forms of hepatic autoimmunity, and risk for both diseases has a strong genetic component. This study aimed to define the genetic architecture of PBC and PSC within the Polish population.MethodsSubjects were 443 women with PBC, 120 patients with PSC, and 934 healthy controls recruited from Gastroenterology Departments in various Polish hospitals. Allelotyping employed a pooled-DNA sample-based genome-wide association study (GWAS) approach, using Illumina Human Omni2.5-Exome BeadChips and the following novel selection criteria for risk loci: blocks of at least 10 single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium, where the distance between each adjacent SNP pair in the block was less than 30 kb, and each SNP was associated with disease at a significance level of P < 0.005. A selected index SNP from each block was validated using TaqMan SNP genotyping assays.ResultsNineteen and twenty-one SNPs were verified as associated with PBC and PSC, respectively, by individual genotyping; 19 (10/9, PBC/PSC) SNPs reached a stringent (corrected) significance threshold and a further 21 (9/12, PBC/PSC) reached a nominal level of significance (P < 0.05 with odds ratio (OR) > 1.2 or < 0.83), providing suggestive evidence of association. The SNPs mapped to seven (1p31.3, 3q13, 6p21, 7q32.1, 11q23.3, 17q12, 19q13.33) and one (6p21) chromosome region previously associated with PBC and PSC, respectively. The SNP, rs35730843, mapping to the POLR2G gene promoter (P = 1.2 × 10-5, OR = 0.39) demonstrated the highest effect size, and was protective for PBC, whereas for PSC respective SNPs were: rs13191240 in the intron of ADGRB3 gene (P = 0.0095, OR = 0.2) and rs3822659 (P = 0.0051, OR = 0.236) along with rs9686714 (P = 0.00077, OR = 0.2), both located in the WWC1 gene.ConclusionsOur cost-effective GWAS approach followed by individual genotyping confirmed several previously identified associations and discovered new susceptibility loci associated with PBC and/or PSC in Polish patients. However, further functional studies are warranted to understand the roles of these newly identified variants in the development of the two disorders.

Influence of chlorinated water on the development of allergic diseases – An overview

Indoor swimming pools can be used all year round and serve for one of the most popular sport pursued for recreation. The positive effect of swimming arises in particular from the involvement of all the muscles of the body, decreasing the burden on the joints, as well as functional improvement of both the lungs and heart. Chlorine is typically used to disinfect swimming pool water and as a result the changes that take place lead to the formation of by-products, such as monochloramines (NH2Cl), dichloramines (NH2Cl2) i trichloramines (NH2Cl3), trihalogenometans (THM) or haloacetic acid (HAA). The highest concentration of these substances is just above the water surface and they may cause irritation of skin, eyes and mucosa of the respiratory tract. The toxic effect of high chlorine concentration and its side-products on the respiratory system is known, but the effect of low concentrations of these compounds is still not fully determined. Recent studies suggest that development of allergic diseases among swimmers may be increased by epithelial disorders driven by airway barrier dysfunction caused by chlorine irritation. Swimming in chlorinated water may be linked to symptoms of bronchial hyperreactivity, asthma and rhinitis especially in children, elite swimmers and employees of indoor swimming pools. Hypersensivity pneumonitis related to the use of swimming pools may manifest as a swimming pool or sauna user lung, most commonly caused by water polluting pathogens. The article summarizes recent data concerning the influence of chlorinated water on the development of allergic diseases.

The influence of a 3-week body mass reduction program on the metabolic parameters and free amino acid profiles in adult Polish people with obesity

BACKGROUND Previous studies have showed differences in the amino acid (AA) composition in the plasma of people with obesity when compared to lean individuals, but the perturbations of AA concentrations in obesity and the dynamics of AA changes after weight loss is not fully understood. OBJECTIVES The objective of the study was to evaluate the effect of a short-term weight reduction program on the metabolic status and plasma AA levels in individuals with obesity. MATERIAL AND METHODS A total of 24 adult Polish patients with a BMI between 34 and 49 kg/m2 were enrolled in a 3-week controlled body mass reduction program based on everyday physical activity and a hypocaloric diet (25-30% less than total daily energy requirements). At baseline and after the program, anthropometric measurements, biochemical parameters and free AA profiles were determined. RESULTS After the weight loss program, significant changes in body mass and metabolic parameters (e.g., low-density lipoprotein, triglyceride, fasting glucose, and insulin levels) were observed. Positive changes in a homeostatic model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) following the program were also found. The levels of 10 AAs (α-amino-n-butyric acid, alanine, citrulline, glutamine, glycine, hydroxyproline, isoleucine, proline, sarcosine, and threonine) had significantly increased following weight loss. Only aspartic acid was present at a significantly lower concentration after the program. CONCLUSIONS Using a 3-week controlled body mass reduction program based on physical activity and a hypocaloric diet, we were able to demonstrate significant changes in biochemical parameters and free AA profiles. To better understand these changes, future studies should involve a long-term program with more patients.