The effects of exposure to and timing of a choline-deficient diet during pregnancy and early postnatal life on the skeletal muscle transcriptome of the offspring.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is related to muscle loss, but the precise mechanism underlying this association remains unclear. The aim of the present study was thus to determine the influence of maternal fatty liver and dietary choline deficiency during pregnancy and/or lactation periods on the skeletal muscle gene expression profile among 24-day-old male rat offspring. METHODS: Histological examination of skeletal muscle tissue specimens obtained from offspring of dams suffering from fatty liver, provided with proper choline intake during pregnancy and lactation (NN), fed a choline-deficient diet during both periods (DD), deprived of choline only during pregnancy (DN), or only during lactation (ND), was performed. The global transcriptome pattern was assessed using a microarray approach (Affymetrix® Rat Gene 2.1 ST Array Strip). The relative expression of selected genes was validated by real-time PCR (qPCR). RESULTS: Morphological differences in fat accumulation in skeletal muscle related to choline supply were observed. The global gene expression profile was consistent with abnormal morphological changes. Mettl21c gene was overexpressed in all choline-deficient groups compared to the NN group, while two genes, Cdkn1a and S100a4, were downregulated. Processes of protein biosynthesis were upregulated, and processes related to cell proliferation and lipid metabolism were inhibited in DD, DN, and ND groups compared to the NN group. CONCLUSIONS: Prenatal and early postnatal exposure to fatty liver and dietary choline deficiency leads to changes in the transcriptome profile in skeletal muscle of 24-day old male rat offspring and is associated with muscle damage, but the mechanism of it seems to be different at different developmental stages of life. Adequate choline intake during pregnancy and lactation can prevent severe muscle disturbance in the progeny of females suffering from fatty liver.

Genetic risk score for gestational weight gain.

Gestational weight gain (GWG) involves health consequences for both mother and offspring. Genetic factors seem to play a role in the GWG trait. For small effect sizes of a single genetic polymorphism (SNP), a genetic risk score (GRS) summarizing risk-associated variation from multiple SNPs can serve as an effective approach to genetic association analysis. The aim of the study was to analyze the association between genetic risk score (GRS) and gestational weight gain (GWG). GWG was calculated for a total of 342 healthy Polish women of Caucasian origin, aged 19 to 45 years. The SNPs rs9939609 (FTO), rs6548238 (TMEM18), rs17782313 (MC4R), rs10938397 (GNPDA2), rs10913469 (SEC16B), rs1137101 (LEPR), rs7799039 (LEP), and rs5443 (GNB3) were genotyped using commercial TaqMan SNP assays. A simple genetic risk score was calculated into two ways: GRS1 based on the sum of risk alleles from each of the SNPs, while GRS2 based on the sum of risk alleles of FTO, LEPR, LEP, and GNB3. Positive association between GRS2 and GWG (ß = 0.12, p = 0.029) was observed. Genetic risk variants of TMEM18 (p = 0.006, OR = 2.6) and GNB3 (p < 0.001, OR = 3.3) are more frequent in women with increased GWG, but a risk variant of GNPDA2 (p < 0.001, OR = 2.7) is more frequent in women with adequate GWG, and a risk variant of LEPR (p = 0.011, OR = 3.1) in women with decreased GWG. GRS2 and genetic variants of TMEM18, GNB3, GNPDA2, and LEPR are associated with weight gain during pregnancy.

Steviol glycosides from Stevia rebaudiana Bertoni mitigate lipid metabolism abnormalities in diabetes by modulating selected gene expression - An in vivo study.

In diabetes, in parallel to hyperglycaemia, elevated serum lipids are also diagnosed, representing a high-risk factor for coronary heart disease and cardiovascular complications. The objective of this study was to unravel the mechanisms that underlie the potential of steviol glycosides (stevioside or rebaudioside A) administered at two doses (500 or 2500 mg/kg body weight for 5 weeks) to regulate lipid metabolism. In this paper, the expression of selected genes responsible for glucose and lipid metabolism (Glut4, Pparγ, Cebpa, Fasn, Lpl and Egr1) in the peripheral tissues (adipose, liver and muscle tissue) was determined using quantitative real-time PCR method. It was found that the supplementation of steviol glycosides affected the expression of Glut4, Cebpa and Fasn genes, depending on the type of the glycoside and its dose, as well as the type of tissue, whish in part may explain the lipid-regulatory potential of steviol glycosides in hyperglycaemic conditions. Nevertheless, more in-depth studies, including human trials, are needed to confirm these effects, before steviol glycosides can be used in the therapy of type 2 diabetes.

The Enhanced Expression of ZWILCH Predicts Poor Survival of Adrenocortical Carcinoma Patients.

Zwilch kinetochore protein (ZWILCH) plays a key role in proper cell proliferation. The upregulation of the ZWILCH gene was observed in many types of cancers, but the association of ZWILCH with adrenocortical carcinoma (ACC) was not investigated so far. The main aim of the presented study was to verify if the enhanced level of the ZWILCH gene can be used as a diagnostic marker for ACC development and progression, as well as a predictor of survival time for ACC patients. The performed analyses included investigation of the ZWILCH expression profile in tumors with publicly available TCGA (The Cancer Genome Atlas) datasets and transcriptomic data from the Gene Expression Omnibus (GEO) database, as well as, in human biological samples of normal adrenal, adrenocortical carcinoma and in commercially available tissue microarrays. The findings demonstrate statistically significant higher ZWILCH gene expression in ACC tissue in comparison with normal adrenal glands. Furthermore, there is a strong correlation between ZWILCH upregulation and tumor mitotic rate and the probability of patient survival. The enhanced ZWILCH level is also connected with the activation of genes involved in cell proliferation and the inhibition of genes related to the immune system. This work contributes to a better understanding of the role of ZWILCH as an ACC biomarker and diagnostic tool.

Functional single-nucleotide polymorphism (rs762551) in CYP1A2 gene affects white coffee intake in healthy 20- to 40-year-old adults.

Coffee is one of the most consumed beverages in the world, but the extent to which it is consumed is affected by both environmental and genetic factors. Genome-wide association studies and candidate date association studies have identified several gene variants associated with increased consumption of coffee. Functional single-nucleotide polymorphisms in rs762551 (cytochrome P450 1A2 [CYP1A2]) and rs5751876 (adenosine receptor A2A [ADORA2A]) has been linked to individual caffeine response. Coffee intake has been shown to affect lipid metabolism. We thus hypothesize that rs762551 (CYP1A2) A allele carriers consume more coffee than C allele carriers and that rs5751876 (ADORA2A) C allele carriers consume less coffee than T allele carriers. Additionally, we hypothesize that CYP1A2 genotype can modulate serum glucose concentrations and lipid profile. A total of 421 participants aged 20 to 40 years were recruited from 2016 to 2018 in Poznan, Poland. Genotyping of CYP1A2 and ADORA2A was performed using TaqMan probes. Individuals with AA CYP1A2 genotype consumed relatively more coffee with milk (72.81 ± 10.15 mL/1000 kcal vs 43.38 ± 6.42 mL/1000 kcal, P = .008) and with milk or cream than did C allele carriers, whereas the rs5751876 ADORA2A polymorphism was not associated with coffee or tea intake. Additionally, subjects with AA CYP1A2 genotype had 10% higher serum triacylglycerol (TG) concentrations than C allele carriers. This study suggests that CYP1A2 rs762551 polymorphism is associated with coffee intake and serum TG concentrations in healthy 20- to 40-year-old adults.

ß-glucuronidase activity is associated with carbohydrate metabolism but not with androgen status in overweight and obese women with polycystic ovary syndrome.

OBJECTIVES: The aim of this study was to evaluate the relationship between ß-glucuronidase and androgen levels in overweight and obese women with polycystic ovary syndrome (PCOS). The connection between ß-glucuronidase, the abundance of selected gut bacteria, carbohydrate metabolism, and diet quality was also determined. METHODS: This cross-sectional study was conducted with 56 women with a mean age of 29.14 ± 5.11 y and a mean body mass index (BMI) of 34.15 ± 5.72 kg/m2. Anthropometrical parameters, fecal ß-glucosidase activity, and selected food frequency intake were measured. RESULTS: Women with better quality diets, apart from lower BMI and better carbohydrate metabolism parameters, had more abundant Faecalibacterium prausnitzii and Akkermansia muciniphila. Two-hour oral glucose tolerance test (OGTT-2h-glu; mg/dL) was the main predictor of ß-glucuronidase activity and there was no relationship between ß-glucuronidase activity and androgen levels. Non-Healthy Diet Index-14 (nHDI-14) was the main predictor for A. muciniphila, Bifidobacteriu. longum, and F. prausnitzii abundance. QUICKI was a significant predictor of A. muciniphila abundance and OGTT-2h-glu was a significant predictor of F. prausnitzii abundance. CONCLUSION: There was no relationship between ß-glucuronidase activity and androgen levels in overweight and obese women with PCOS, but ß-glucuronidase activity may be an important factor in carbohydrate metabolism. Modulation of the abundances of F. prausnitzii, A. muciniphila, and B. longum using special diets should thus be considered a promising intervention.

Greater self-reported preference for fat taste and lower fat restraint are associated with more frequent intake of high-fat food.

The determinants of the intake of high-fat products are not well recognized, but fat preference may be one of them. The aim of this study was thus to determine whether intake of different types of high-fat food is associated with fat preference in people with normal and increased body weight. Participants aged 20-40 years [n = 421] were enrolled in Poznan, Poland in 2016-2018. Fat preference was measured using the Fat Preference Questionnaire. Self-reported preference for fat taste (TASTE) and fat restraint (DIFF) scores were calculated. The frequency of consuming high-fat food was measured with an application for mobile devices using ecological momentary assessment. TASTE was positively associated with calorie intake and total frequency of eating high-fat food in both the normal weight and the overweight/obese groups. Overweight and obese people had lower DIFF (p < 0.001) than normal weight people. DIFF was negatively associated with total calorie intake and total intake of high-fat food, but only in normal weight people (ß = -0.16, p < 0.01 and ß = -0.26, p < 0.001, respectively). DIFF was negatively associated with the frequency of eating sweet (ß = -0.33, p < 0.000) and meat high-fat food (ß = -0.25, p < 0.001) in the normal weight group. The frequency of consumption of high-fat food and calorie intake are positively associated with self-reported preference for fat taste. In normal weight subjects fat restraint is negatively associated with calorie intake and total frequency of high-fat food intake, as well as with intake of different types of fatty food. Fat preference measures are thus associated with high-fat food intake, but these associations differ by body weight status.

Polymorphism of CD36 Determines Fat Discrimination but Not Intake of High-Fat Food in 20- to 40-Year-Old Adults.

BACKGROUND: The determinants of the intake of high-fat products are not well understood. OBJECTIVE: The aim of this study was to examine the relations between fat perception, intake of high-fat food, and body-weight status, taking into account the polymorphism of the genes that encode the proteins involved in oral fat perception. METHODS: A total of 421 participants aged 20-40 y were enrolled in Poznan, Poland, from 2016 to 2018. An ascending forced-choice triangle procedure was applied to determine fat discrimination ability. Salad dressings with varying concentrations of canola oil were used as stimuli. Genotyping of rs1761667 (CD36) rs1573611 [free fatty acid receptor 1 (FFAR1)], rs17108973 [free fatty acid receptor 4 (FFAR4)], and rs2274333 (CA6) was performed using TaqMan probes. The frequency of consumption of high-fat foods was measured using an application for mobile devices that uses the ecological momentary assessment approach. The associations were analyzed using linear regression or logistic regression, as appropriate. RESULTS: Individuals with the GG CD36 genotype were twice as likely to be fat discriminators, compared with the A allele carriers (P < 0.05). The mean total consumption of high-fat food was 45.8 (44.6, 47.0) times/wk and was not associated with fat discrimination or body-weight status. Obese and overweight subjects ate healthy high-fat food less frequently than did participants with normal body weight, at 4.53 (3.83, 5.23) versus 6.68 (5.82, 7.55) times/wk, respectively (P < 0.001). Men ate sweet high-fat food and snacks 15% less frequently than did women (P < 0.001 and P < 0.05) but consumed high-fat meat and fast food almost 40% more often than did women (P < 0.001 for both associations). CONCLUSIONS: In individuals aged 20-40 y, fat discrimination ability is associated with polymorphism of CD36 but not with the choice of high-fat food. The frequency of consumption of different types of high-fat foods varies by sex and body-weight status.

Polymorphism of TAS2R3, TAS2R5, TAS2R19, and TAS2R50 genes and bitter food intake frequency inelderly woman.

BACKGROUND: Taste sensitivity is one of the most important biological determinants of food choice. Polymorphisms within the bitter taste receptor genes TAS2R3 (rs765007), TAS2R5 (rs2234012), TAS2R19 (rs10772420), and TAS2R50 (rs1376251) may affect bitter taste sensitivity and thus food choices and thereby metabolic biomarkers in blood. The aim of this study was to investigate associations between selected TAS2Rs  single nucleotide polymorphisms (SNPs) and the choice of the most popular bitter food items in    a Polish population, BMI and blood biomarkers in elderly women. METHODS: The study group included 116 Polish women over 60 years of age. Intake of Brassica vegetables, grapefruit and coffee was assessed using a food frequency questionnaire. Biochemical parameters were measured using the spectrophotometric method. Genotyping was performed using the high resolution melting method. RESULTS: We show an association between SNPs of the TAS2R3 gene and the frequency of Brassica vegetable intake, between SNPs of the TAS2R5 gene and the frequency of grapefruit intake, and between the simultaneous effects of polymorphisms within TAS2R3 and TAS2R5 and the frequency of eating Brassica vegetables in general. We found no association between the genetic polymorphisms of TAS2R19 or TAS2R50 that were examined and the frequency of bitter-tasting food intake. Moreover, the SNPs of the selected TAS2Rs genes may be associated with the lipid profile, serum level of glucose and CRP, depending on the frequency of consumption of particular bitter-tasting items. CONCLUSIONS: The genetic polymorphisms analyzed in the study seem not to contribute significantly to variability in bitter-tasting food intake in elderly women, although they may influence metabolic biomarkers dependent on the intake of particular bitter-tasting food items.

TAS2R38 and CA6 genetic polymorphisms, frequency of bitter food intake, and blood biomarkers among elderly woman.

OBJECTIVE: Taste sensitivity is one of the most important biological determinants of food choice. Three SNPs of the TAS2R38 gene (rs713598, rs1726866, and rs10246939) give rise to two common haplotypes: PAV and AVI. These haplotypes, as well as an SNP within the CA6 gene (rs2274333) that encodes carbonic anhydrase VI (CA6), correlate with bitterness perception. The extent of consumption of bitter food may influence some health outcomes. The aim of this study is thus to investigate the impact of the TAS2R38 and CA6 genetic polymorphisms on the choice of bitter food, BMI, blood lipoprotein, and glucose concentrations as well as systemic inflammation in elderly women. METHODS: The associations between the TAS2R38 diplotype, CA6 genotype, and the intake of bitter-tasting foods were studied in a group of 118 Polish women over 60 years of age. The intake of Brassica vegetables, grapefruit, and coffee was assessed using a food frequency questionnaire. Biochemical parameters were measured using the spectrophotometric method. Genotyping was performed using the high resolution melting method. RESULTS: We found a correlation between lipid profile, glucose and CRP levels, and frequency of bitter food intake. The AVI/AVI subjects drank coffee more frequently than did the PAV/PAV homozygotes, as did the A carriers of CA6 in comparison with the GG homozygotes. We also observed that simultaneous carriers of the PAV haplotype and A allele of TAS2R38 and CA6, respectively, choose white cabbage more frequent and had lower plasma levels of CRP and glucose than did AVI/AVI and GG homozygotes. CONCLUSIONS: In elderly women, the TAS2R38 and CA6 polymorphisms may affect the frequency of consumption of coffee and white cabbage, but not of other bitter-tasting foods.

Gene polymorphism -418 G/C of tissue inhibitor of metalloproteinases 2 is associated with abdominal aortic aneurysm.

OBJECTIVE: The pathogenesis of abdominal aortic aneurysm (AAA) is connected with abnormal extracellular matrix remodeling, with the assistance of extracellular matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). A decrease in tissue inhibitor of metalloproteinases 2 (TIMP2) gene expression was detected in AAA patients. Recently, a -418 G/C (rs8179090) polymorphism of the TIMP2 gene promoter, influencing the transcription rate of the gene, has been described. This study investigated whether the -418 G/C gene polymorphism is associated with AAA in the Polish population. METHODS: The TIMP2 gene promoter polymorphism was evaluated by polymerase chain reaction, followed by restriction enzyme analysis and pyrosequencing in 128 patients affected by AAA and in 180 individuals included as references. The control group was directly matched to patients according to known risk factors for vascular diseases. RESULTS: The frequency of the C allele was significantly higher in AAA patients than in the control group (odds ratio [OR], 2.516; P = .0005). The distribution of genotypes also differed significantly between the groups (CC + CG vs GG: OR, 2.906; P = .0037) or was close to being significantly different (CC vs GG + GC: OR, 2.144; P = .0501). A similar trend was observed in men but not in women. The multivariate logistic regression analysis indicated the TIMP2 gene promoter polymorphism is risk factor of AAA in the Polish population, with an adjusted OR of 4.99, when applied to a dominant inheritance model. CONCLUSIONS: Our study supports the hypothesis that TIMP2 and the -418G/C polymorphism located in the promoter of the TIMP2 gene are important in AAA pathophysiology.

Risk factors in abdominal aortic aneurysm and in Polish population aortoiliac occlusive disease and differences between them [corrected].

Abdominal aortic aneurysm (AAA) and aortoiliac occlusive disease (AIOD) are multifactorial vascular disorders caused by complex genetic and environmental factors. The purpose of this study was to define risk factors of AAA and AIOD in the Polish population and indicate differences between diseases.

Interleukin-1 gene polymorphisms in chronic gastritis patients infected with Helicobacter pylori as risk factors of gastric cancer development.

Epidemiological investigations indicated association of the Helicobacter pylori infections with the occurrence of inflammatory conditions of the gastric mucosa and development of chronic gastritis and intestinal type of gastric cancer. IL1A and IL1B genes have been proposed as key factors in determining risk of gastritis and malignant transformation. The aim of this paper was to evaluate association of interleukin-1 gene polymorphisms with chronic gastritis, atrophy, intestinal metaplasia, dysplasia and intestinal type of gastric cancer in H. pylori-infected patients. Patients subjected to analysis represent group of 144 consecutive cases that suffered from dyspepsia with coexisting infection of H. pylori and chronic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia or gastric cancer. Molecular studies involved analysis of -889C>T polymorphism of IL1A gene and +3954C>T polymorphism of IL1B gene. Statistical analysis of association of polymorphism -889C>T of gene IL1A with changes in gastric mucosa showed lack of significance, whereas +3954C>T polymorphism of IL1B gene showed significant association. Frequency of allele T of +3954C>T polymorphism of IL1B gene was higher in group of patients with chronic gastritis, atrophy, intestinal metaplasia, dysplasia or intestinal type of gastric cancer (32.1 %) as compared with population group (23 %), χ(2) = 4.61 and p = 0.03. This corresponds to odds ratio: 1.58, 95 % CI: 1.04-2.4. Our results indicate that +3954C>T polymorphism of IL1B gene increase susceptibility to inflammatory response of gastric mucosa H. pylori-infected patients and plays a significant role in the development of chronic gastritis, atrophy, intestinal metaplasia, dysplasia and the initiation of carcinogenesis.

Angiotensin-converting enzyme (ACE, I/D) gene polymorphism and susceptibility to abdominal aortic aneurysm or aortoiliac occlusive disease.

BACKGROUND: The purpose of this study was to examine the role of polymorphism in angiotensin converting enzyme gene (ACE, I/D) in the development of abdominal aortic aneurysm (AAA) or aortoiliac occlusive disease (AIOD). MATERIALS AND METHODS: We investigated 829 individuals in 4 groups: AAA (n = 133), AIOD (n = 152), control (n = 152), and a random Polish population group (n = 392). ACE I/D gene polymorphism analysis was performed by polymerase chain reaction and gel electrophoresis. The genotype distribution was in Hardy-Weinberg equilibrium. RESULTS: The genotype distribution and allele frequency of ACE I/D were not significantly different between patients with AAA or AIOD and the control or the population group. Significant differences were found between the following groups: 1) hypertensive patients with AAA and normotensive patients with AAA (OR = 3.08 95% CI 1.22-7.79, P = 0.0147); 2) hypertensive patients with AAA and the population group (OR = 2.56; 95% CI 1.27-5.16, P = 0.0066). Since the majority of subjects were male, these associations were also true when only male hypertensive subjects with AAA were compared with male normotensive patients with AAA or to male population group. No relation of the ACE gene polymorphism to hypertension in the AIOD group was found. CONCLUSIONS: ACE I/D gene polymorphism is not a susceptibility factor to aortoiliac occlusive disease; however it may be an important factor in the development of AAA when coexisting with hypertension.