Patrycja Krzyżanowska

Mild CFTR mutations and genetic predisposition to lactase persistence in cystic fibrosis

Taking into account the reported incidence of hypolactasia in cystic fibrosis (CF) and the possible impact of milk products on nutritional status we aimed to assess the genetic predisposition to adult-type hypolactasia (ATH) and its incidence in CF. Single nucleotide polymorphism upstream of the lactase gene (LCT) was assessed in 289 CF patients. In subject with −13910C/C genotype (C/C) predisposing to ATH, hydrogen-methane breath test (BT) with lactose loading was conducted and clinical symptoms typical for lactose malabsorption were assessed. The percentage of CF patients with C/C was similar to that observed in healthy subjects (HS) (31.5 vs 32.5% ). Eleven out of 52 (24.5%) CF C/C patients had abnormal BT results. The recalculated frequency of lactose malabsorption was similar for the entire CF and HS populations (6.9 vs 7.2%). Similarly as in the control group, few CF patients have identified and linked to lactose consumption clinical symptoms. The frequency of LCT polymorphic variants in CF patients having and not having severe mutations of CFTR gene showed significant differences. The C allele was more frequent in homozygotes of the severe mutations than in patients carrying at least one mild/unknown mutation (P<0.0028) and in patients with at least one mild mutation (P<0.0377). In conclusion, CF patients carrying mild CFTR mutations seem to have lower genetic predisposition to ATH. Lactose malabsorption due to ATH in CF is not more frequent than in the general population. Symptomatic assessment of lactose malabsorption in CF is not reliable.

Exogenous and endogenous determinants of vitamin K status in cystic fibrosis.

Cystic fibrosis (CF) patients are at high risk for vitamin K deficiency. The effects of vitamin K supplementation are very ambiguous. Therefore, we aimed to define the determinants of vitamin K deficiency in a large cohort of supplemented - 146 (86.9%) and non-supplemented - 22 (13.1%) CF patients. Vitamin K status was assessed using prothrombin inducted by vitamin K absence (PIVKA-II) and undercarboxylated osteocalcin (u-OC). The pathological PIVKA-II concentration (≥2 ng/ml) and abnormal percentage of osteocalcin (≥20%) were found in 72 (42.8%) and 60 (35.7%) subjects, respectively. We found that liver involvement, diabetes, and glucocorticoid therapy were potential risk factors for vitamin K deficiency. Pathological concentrations of PIVKA-II occurred more frequently in patients with pancreatic insufficiency and those who have two severe mutations in both alleles of the CFTR gene. Pathological percentage of u-OC was found more frequently in adult CF patients and those not receiving vitamin K. However, it seems that there are no good predictive factors of vitamin K deficiency in CF patients in everyday clinical care. Early vitamin K supplementation in CF patients seems to be warranted. It is impossible to clearly determine the supplementation dose. Therefore, constant monitoring of vitamin K status seems to be justified.

Weight loss and metabolic health effects from energy-restricted Mediterranean and Central-European diets in postmenopausal women: A randomized controlled trial

We conducted a randomized controlled trial to examine the effect of two energy-restricted diets on body weight (BW), visceral fat (VF) loss, and the risk factors for metabolic syndrome. A total of 144 centrally obese postmenopausal women were assigned to the moderate in fat Mediterranean diet (MED) or to the Central European diet (CED), which is moderate in carbohydrates and high in dietary fiber (DF), for 16 weeks. BW, waist circumference and VF were significantly reduced by 8.8%, 7.0%, and 24.6%, respectively, over the trial (P < 0.001), with no difference between groups. A similar trend was seen for total cholesterol, triglycerides, glucose, and blood pressure. Within each diet group, the more adherent participants lost significantly more BW than did their less adherent counterparts. VF was significantly reduced only in women who were more adherent to the CED, and the reduction in VF correlated with an increase in the proportion of DF. Short-term dietary treatment with the CED or the MED was associated with similar improvements in some anthropometric, lipid, and nonlipid parameters; however, adequate adherence to the prescribed diet is important in weight loss success and in achieving improvements in metabolic health.

Determinants of Serum Glycerophospholipid Fatty Acids in Cystic Fibrosis

The etiology of altered blood fatty acid (FA) composition in cystic fibrosis (CF) is understood only partially. We aimed to investigate the determinants of serum glycerophospholipids’ FAs in CF with regard to the highest number of FAs and in the largest cohort to date. The study comprised 172 CF patients and 30 healthy subjects (HS). We assessed Fas’ profile (gas chromatography/mass spectrometry), CF transmembrane conductance regulator (CFTR) genotype, spirometry, fecal elastase-1, body height and weight Z-scores, liver disease, diabetes and colonization by Pseudomonas aeruginosa. The amounts of saturated FAs (C14:0, C16:0) and monounsaturated FAs (C16:1n-7, C18:1n-9, C20:1n-9, C20:3n-9) were significantly higher in CF patients than in HS. C18:3n-6, C20:3n-6 and C22:4n-6 levels were also higher in CF, but C18:2n-6, C20:2n-6 and C20:4n-6, as well as C22:6n-3, were lower. In a multiple regression analysis, levels of seven FAs were predicted by various sets of factors that included age, genotype, forced expiratory volume in one second, pancreatic status and diabetes. FA composition abnormalities are highly prevalent in CF patients. They seem to be caused by both metabolic disturbances and independent clinical risk factors. Further research into the influence of CFTR mutations on fat metabolism and desaturases’ activity is warranted.

Vitamin K status in cystic fibrosis patients with liver cirrhosis

The available data on the influence of liver cirrhosis on vitamin K status in CF patients is scarce. Therefore, the aims of the present study were to assess the prevalence of vitamin K deficiency in cirrhotic CF subjects and to determine whether it correlates with liver cirrhosis. The study group comprised of 27 CF patients with and 63 without liver cirrhosis. Vitamin K status was assessed using prothrombin induced by vitamin K absence (PIVKA-II) and the percentage of undercarboxylated osteocalcin (u-OC). PIVKA-II concentrations were higher in cirrhotic than in non-cirrhotic CF patients (median [1st-3rd quartile]: 3.2ng/ml [1.0-10.0] vs. 1.3ng/ml [0.2-2.6], p=0.0029). However, the differences in u-OC percentages between the studied groups did not reach the level of significance (49.4% [7.0-73.8] vs. 8.0% [2.6-59.1], p=0.0501). Based on multiple linear regression analysis the dose of vitamin K and F508del mutation were potentially defined as determinants of vitamin K deficiency. Liver cirrhosis was not documented to be an independent risk factor. In CF patients with liver cirrhosis vitamin K deficiency is not only more frequent, but also more severe. However, not liver cirrhosis, but the presence of a F508del CFTR mutation constitutes an independent risk factor for vitamin K deficiency.

International Symposium on Immunonutrition 2017, Madrid, 17th-19th July, 2017, 10th Anniversary: Abstracts

3 p.International Symposium on Immunonutrition 2017 Madrid, 17th–19th July, 2017 10th Anniversary

Twelve-week-conjugated linoleic acid supplementation has no effects on the selected markers of atherosclerosis in obese and overweight women.

Background The antiatherogenic effect of conjugated linoleic acid (CLA) has been demonstrated in animal models. Although there are plenty of in vitro studies that suggest the profitable properties of CLA, the results in humans remain inconsistent. Objective In this study, we assessed the impact of CLA supplementation on the levels of atherosclerosis markers – high-sensitivity C-reactive protein (hs-CRP) and asymmetrical dimethylarginine (ADMA). Design Seventy-four adult female subjects with body mass index ≥25 kg/m2 were enrolled in the double-blind, placebo-controlled nutritional intervention. The study participants were randomly assigned to receive 3 g/day CLA or placebo (sunflower oil) for 12 weeks. In all subjects, we measured hs-CRP and ADMA concentrations by using enzyme-linked immunosorbent assay. Results No significant differences were found in hs-CRP and ADMA levels before and after nutritional intervention between both groups. The changes in hs-CRP and ADMA concentration values (Δhs-CRP; ΔADMA median [interquartile range]) did not differ between subjects from the placebo (−0.1 [−0.8 to 0.3]; −0.02 [−0.12 to 0.14]) and CLA (0.2 [−0.7 to 0.9]; 0.04 [−0.14 to 0.13]) groups. The incidence of reduction of hs-CRP or ADMA concentration was not different in subjects of the CLA group compared to those of the placebo group (41.9% vs. 50%, relative risk [RR]=0.8387, 95% confidence interval [CI]=0.4887–1.4493, p=0.5232 and 61.3% vs. 56.2%, RR=1.0896, 95% CI=0.7200–1.6589, p=0.6847, respectively). Conclusion Twelve weeks of CLA supplementation had no effect on selected markers of atherosclerosis in obese and overweight women.

Stanowisko Polskiego Towarzystwa Mukowiscydozy (PTM) dotyczące wykonania klasycznego testu potowego

Streszczenie Proba potowa jest waznym testem laboratoryjnym stanowiącym podstawe diagnostyki mukowiscydozy. Jego prawidlowe wykonanie jest zatem niezwykle istotne. W pracy przedstawiono zasady wykonania proby potowej, podając dane dotyczące symulacji pocenia oraz zbierania potu. Jednocześnie odniesiono sie do rekomendacji i wytycznych miedzynarodowych towarzystw i gremiow.

Znaczenie witaminy K w mukowiscydozie

Streszczenie Mukowiscydoza (cystic fibrosis – CF) jest najcześciej wystepującą w populacji kaukaskiej chorobą genetyczną o autosomalnym recesywnym typie dziedziczenia. Jej przyczyną są mutacje genu CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), zlokalizowanego na dlugim ramieniu chromosomu 7. Produktem powyzszego genu jest bialko CFTR, spelniające role kanalu chlorkowego, ktore jest obecne na szczytowej powierzchni komorek nablonkowych wydzielania zewnetrznego. Efektem mutacji genu CFTR jest brak funkcjonalnego bialka, co w konsekwencji prowadzi do gromadzenia lepkiego śluzu w wielu narządach ukladu oddechowego i pokarmowego. Chorzy na CF są narazeni na niedobor witaminy K z powodu: zaburzen wchlaniania tluszczow (niewydolnośc zewnątrzwydzielnicza trzustki), chorob wątroby, czestych antybiotykoterapii oraz resekcji fragmentu jelita cienkiego w przebiegu niedrozności smolkowej. Witamina K jest kofaktorem posttranslacyjnej gamma-karboksylacji reszt kwasu glutaminowego do reszt kwasu gamma-karboksyglutaminowego. Do bialek zaleznych od witaminy K zalicza sie osteokalcyne, bialka C, S, Z oraz czynniki krzepniecia krwi: II, VII, IX, X. Z tego powodu odpowiada ona za utrzymanie hemostazy oraz mineralizacje koścca. W przypadku niedoboru witaminy K wyzej wymienione bialka wystepują w formach niekarboksylowanych i nie spelniają swojej biologicznej funkcji. Ich pojawienie sie jest natomiast czulym wskaźnikiem niedoboru powyzszej witaminy. Chorzy na CF są zdecydowanie bardziej narazeni na wystąpienie osteopenii spowodowanej dlugotrwalym niedoborem witaminy K niz koagulopatii. W świetle dostepnej wiedzy, jej suplementacja wydaje sie niezbedna.

Współwystępowanie celiakii u chorych na mukowiscydozę

Streszczenie Mukowiscydoza (CF) jest najcześciej wystepującą w populacji kaukaskiej chorobą genetyczną o autosomalnym recesywnym typie dziedziczenia. Jej przyczyną są mutacje genu CFTR (cystic fibrosis transmembrane conductance regulator), zlokalizowanego na dlugim ramieniu chromosomu 7. Produktem powyzszego genu jest bialko CFTR, spelniające role kanalu chlorkowego. Efektem mutacji genu CFTR jest brak funkcjonalnego bialka, co w konsekwencji prowadzi do gromadzenia lepkiego śluzu w wielu narządach. Dlatego choroba w glownej mierze dotyczy ukladu oddechowego oraz pokarmowego. Celiakia (CD) jest autoimmunologiczną chorobą jelita cienkiego. Spowodowana jest nadmierną odpowiedzią immunologiczną na gluten. Do jej klasycznych objawow nalezą: przewlekla biegunka, zahamowanie wzrostu, ubytek masy ciala, zaburzenia laknienia, obrzeki, krzywica, czeste infekcje ukladu oddechowego oraz opoźnienie psychoruchowe. Postac nieklasyczna z lagodniejszymi objawami wystepuje jednak znacznie cześciej. Wiele z tych objawow klinicznych moze wystepowac zarowno w CD, jak i CF. Dlatego tez, w przeszlości obydwie jednostki chorobowe byly czesto mylone. Wprowadzenie nowych metod diagnostycznych, w tym technik molekularnych, ulatwilo ustalenie wlaściwej diagnozy. W pracy przedstawiono podstawowe informacje dotyczące CD i CF, a takze opisano i przedyskutowano ich wspolistnienie.