GG Group Research Articles

The Prophylactic Effects of Glutamine on Muscle Protein Synthesis and Degradation in Rats with Ethanol-Induced Liver Damage.

The purpose of this research was to investigate the prophylactic effects of glutamine on muscle protein synthesis and degradation in rats with ethanol-induced liver injury. For the first 2 weeks, Wistar rats were divided into two groups and fed a control (n = 16) or glutamine-containing diet (n = 24). For the following 6 weeks, rats fed the control diet were further divided into two groups (n = 8 per group) according to whether their diet contained no ethanol (CC) or did contain ethanol (CE). Rats fed the glutamine-containing diet were also further divided into three groups (n = 8 per group), including a GG group (glutamine-containing diet without ethanol), GE group (control diet with ethanol), and GEG group (glutamine-containing diet with ethanol). After 6 weeks, results showed that hepatic fatty change, inflammation, altered liver function, and hyperammonemia had occurred in the CE group, but these were attenuated in the GE and GEG groups. Elevated intestinal permeability and a higher plasma endotoxin level were observed in the CE group, but both were lower in the GE and GEG groups. The level of a protein synthesis marker (p70S6K) was reduced in the CE group but was higher in both the GE and GEG groups. In conclusion, glutamine supplementation might elevate muscle protein synthesis by improving intestinal health and ameliorating liver damage in rats with chronic ethanol intake.

Antioxidative Defense Genes and Brain Structure in Youth Bipolar Disorder.

BackgroundOxidative stress is implicated in the neuropathology of bipolar disorder (BD). We investigated the association of single-nucleotide polymorphisms (SNPs) in the antioxidative genes superoxide dismutase 2 (SOD2) and glutathione peroxidase 3 (GPX3) with structural neuroimaging phenotypes in youth BD.Methods SOD2 rs4880 and GPX3 rs3792797 SNP genotypes, along with structural magnetic resonance imaging, were obtained from 147 youth (BD = 75; healthy controls = 72). Images were processed using FreeSurfer, yielding surface area, volume, and thickness values for regions of interest (prefrontal cortex [PFC], caudal anterior cingulate cortex, hippocampus) and for vertex-wise whole-brain analysis. Analyses controlled for age, sex, race, and intracranial volume for volume, area, and thickness analyses.ResultRegions of interest analyses revealed diagnosis-by-SOD2 rs4880 interaction effects for caudal anterior cingulate cortex volume and surface area as well as PFC volume; in each case, there was lower volume/area in the BD GG genotype group vs the healthy controls GG genotype group. There was a significant BD diagnosis × GPX3 rs3793797 interaction effect for PFC surface area, where area was lower in the BD A-allele carrier group vs the other genotype groups. Vertex-wise analyses revealed significant interaction effects in frontal, temporal, and parietal regions related to smaller brain structure in the BD SOD2 rs4880 GG group and BD GPX3 rs3793797 A-allele carrier group.ConclusionWe found preliminary evidence that SOD2 rs4880 and GPX3 rs3792797 are differentially associated with brain structures in youth with BD in regions that are relevant to BD. Further studies incorporating additional neuroimaging phenotypes and blood levels of oxidative stress markers are warranted.

Characterization of Genetic Variants in the SLC5A5 Gene and Associations With Breast Milk Iodine Concentration in Lactating Women of African Descent: The NUPED Study.

Background: The sodium iodide symporter is responsible for the transfer of iodine into breast milk and is encoded for by the SLC5A5 gene. The role of genetic variants in the SLC5A5 gene locus in relation to the transfer of iodine from plasma into breast milk in healthy lactating individuals has, to our knowledge, not been explored.Objective: To identify and characterize possible genetic variants of the SLC5A5 gene in women of African descent living in urban South Africa, and to study associations with breast milk iodine concentrations (BMIC) in lactating women.Methods: This study is affiliated to the Nutrition during Pregnancy and Early Development (NuPED) cohort study (n = 250 enrolled pregnant women). In a randomly selected sub-sample of 32 women, the SLC5A5 gene was sequenced to identify known and novel variants. Of the identified variants, genotyping of selected variants was performed in all pregnant women who gave consent for genetic analyses (n = 246), to determine the frequency of the variants in the study sample. Urinary iodine concentration (UIC) in spot urine samples and BMIC were measured to determine iodine status. Associations of SLC5A5 genetic variants with BMIC were studied in lactating women (n = 55).Results: We identified 27 variants from sequencing of gene exomes and 10 variants were selected for further study. There was a significant difference in BMIC between the genotypes of the rs775249401 variant (P = 0.042), with the homozygous GG group having lower BMIC [86.8 (54.9–167.9) μg/L] compared to the (A) allele carriers rs775249401(AG+AA) [143.9 (122.4–169.3) μg/L] (P = 0.042). Of the rs775249401(GG), 49% had UIC <100 μg/L and 61% had BMIC <100 μg/L. On the other hand, 60% of the rs775249401(AG+AA) carriers had UIC <100 μg/L, and none had a BMIC <100 μg/L.Conclusion: Our results suggest that A-allele carriers of rs775249401(AG+AA) are likely to have higher iodine transfer into breast milk compared to the homozygous GG counterparts. Thus, genetic variations in the SLC5A5 gene may play an important role in the transfer of iodine from plasma into breast milk and may partially explain inter-individual variability in BMIC.

Beneficial effect of dietary geranylgeraniol on glucose homeostasis and bone microstructure in obese mice is associated with suppression of proinflammation and modification of gut microbiome

Geranylgeraniol (GGOH) is found in edible oils such as olive, linseed, and sunflower oils, which have favorable metabolic effects. However, it is unknown whether these physiological benefits are mediated through the gut microbiome. Thus, the purpose of this study was to test the hypothesis that GGOH supplementation would improve glucose homeostasis and benefit the bone microstructure in obese mice through suppression of inflammation and modification of gut microbiota composition. Thirty-six male C57BL/6J mice were divided into 3 groups: a low-fat diet, a high-fat diet (HFD), and an HFD supplemented with 800 mg GGOH/kg diet (GG) for 14 weeks. Glucose and insulin tolerance tests were measured at baseline and end of study. The concentrations of adipokine cytokines (resistin, leptin, monocyte chemoattractant protein-1, interleukin-6) were measured via ELISA. Bone microarchitecture and quality were measured by micro-CT. Microbiome analysis was performed using 16S rRNA amplicon sequencing on cecal content. Relative to the HFD group, the GG group: (1) improved glucose tolerance and insulin sensitivity; (2) reduced production of pro-inflammatory adipokines, (3) increased serum procollagen I intact N-terminal propeptide (bone formation marker) concentrations, while decreasing serum collagen type 1 cross-linked C-telopeptide (bone resorption marker) levels, and (4) increased stiffness at both femur and LV-4 and cortical thickness at femoral midshaft. Compared to the HFD group, the GG group had an increased abundance of Butyricicoccus pullicaecorum and decreased Dorea longicatena in the cecal microbiome. Collectively, GGOH improves glucose homeostasis and bone microstructure in obese mice, probably via suppression of pro-inflammation and modification of microbiome composition.

Caveolin-1 genetic polymorphism interacts with PUFA to modulate metabolic syndrome risk.

Several studies have reported a significant association between the metabolic syndrome (MetS) and mortality around the world. Caveolin-1 (CAV-1) has been widely studied in dyslipidaemia, and several studies have indicated that CAV-1 genetic variations may correlate with dietary intake of fatty acids. This study aimed to investigate the interaction of CAV-1 rs3807992 with types of dietary fatty acid in the MetS risk. This cross-sectional study was carried out on 404 overweight and obese females. Dietary intake was obtained from a 147-item FFQ. The CAV-1 genotype was measured using the PCR-restriction fragment length polymorphism method. Anthropometric values and serum levels (TC, LDL, HDL, TAG and FBS) were measured by standard methods. It was observed that the (AA + AG) group had significantly higher BMI, waist circumference and DBP (P = 0·02, P = 0·02, and P = 0·01, respectively) and lower serum LDL, HDL and TC (P < 0·05) than the GG group. It was found that A allele carriers were at higher odds of the MetS (P = 0·01), abdominal obesity (P = 0·06), increased TAG concentration (P = 0·01), elevated blood pressure (BP) (P = 0·01), increased glucose concentration (P = 0·45) and decreased HDL-cholesterol concentration (P = 0·03). Moreover, the interaction of CAV-1 and SFA intake was significant in terms of the MetS (P = 0·03), LDL (P = 0·03) and BP (P = 0·01). Additionally, the (AA + AG) group was significantly related to PUFA intake in terms of the MetS (P = 0·04), TAG (P = 0·02), glucose (P = 0·02) and homoeostasis model assessment insulin resistance (P = 0·01). Higher PUFA consumption might attenuate the CAV-1 rs3807992 associations with the MetS, and individuals with greater genetic predisposition appeared to have a higher risk of the MetS, associated with higher SFA consumption.

Perinatal Outcomes After Undergoing External Cephalic Version

: The external cephalic version (ECV) represents the standard for pregnancies at term with a non-cephalic presentation as it avoids planned caesareans. The aim of this study was to assess the caesarean rate and prognostic factors at birth after undergoing ECV, which was compared with scheduled caesareans for a non-cephalic presentation (SCG) and spontaneous cephalic presentations at birth (GG). No difference was observed between the caesarean rate of the ECV (n=65) and the GG (n=3711) groups (9.84% and 14.47%, respectively, p-value=0.30), and neither was found between the ECV group and both the GG and SCG (n=76) groups in the Apgar scores and postpartum pH, but for the five-minute Apgar score (9.98 and 9.84 in the ECV and SCG groups, respectively, p-value=0.04). This study provides further evidence for clinical practice regarding good perinatal outcomes after undergoing ECV. Further research is required to consistently prove the increase in the intrapartum caesarean rate after ECV that has been previously described in the literature, which has not been found in the present study. Keywords: External Cephalic Version, Breech Presentation, Caesarean Rate, Perinatal Outcomes, Apgar Score, Postpartum Ph.

Influence of carriage of genetic variants CYP2D6 * 4 / CYP2D6 * 3 on maximum heart rate when using bisoprolol in patients with acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Bisoprolol is one of the most effective and frequently prescribed beta-blockers. The widespread use of bisoprolol is due to its high efficiency in the treatment of patients with various cardiological pathologies: arterial hypertension, ischemic heart disease, chronic heart failure. Bisoprolol, like all members of the group of beta-adrenergic blockers, is effective in the treatment of patients with acute myocardial infarction, reducing the risk of complications such as rhythm disturbances and sudden cardiac death. In vitro studies indicate that bisoprolol is a substrate for two isoforms of cytochrome P450 - 3A4 and 2D6. Purpose The purpose of this work was to analyze the effect of CYP2D6 activity on the chronotropic effect of bisoprolol therapy in patients with acute coronary syndrome (ACS). Materials and methods The study included patients with ACS who was assigned bisoprolol according to clinical indications. All patients included in the study were Holter monitor on the 10th day of hospitalization - the minimum, mean, maximum heart rate during the day and the maximum heart rate were assessed at the time of exercise was evaluated against the background of the current therapy. All patients included in the study also underwent molecular genetic testing. The detection of polymorphic variants of СYP2D6 (*3/*4) gene was carried out by real-time PCR. Results A total of 93 patients, 58 males and 35 females were included in the study. The average age of patients is 63 years. In the studied population, CYP2D6 * 3 was not detected. The CYP2D6 * 4 mutation occurred with a frequency of 15%, which is comparable to previously published data on the Russian population. The distribution of alleles corresponded to the Hardy-Weinberg law (Chi square, p&amp;gt; 0.05). In order to determine the effect of genetically determined CYP2D6 activity on the effectiveness of bisoprolol therapy in patients with ACS, we identified a group of patients - carriers of the allelic CYP2D6 * 4 variant in homozygous or heterozygous form (AA / AG) (group with a reduced metabolic rate), and a group with the CYP2D6 genotype GG (group with normal and increased metabolic rate). In the correlation analysis, carriage of CYP2D6 * 4 in heterozygous or homozygous form was associated with a lower maximum heart rate during exercise (r-0.21; p &amp;lt;0.05). Maximum heart rate during exercise in carriers of CYP2D6 * 4 was 107 [105; 119], in the comparison group - 114 [108; 120]. The difference was significant with p &amp;lt;0.05 (values are expressed as median [25%; 75%]). Conclusion In this study, for the first time, the role of the influence of allelic variants of the CYP2D6 gene on the achievement of maximum heart rate during exercise was revealed when using bisoprolol in patients with ACS. These data may have promising implications for maximizing the personalization of therapy for patients, including those with ACS.

A Functional Adenosine Deaminase Polymorphism Associates with Evening Melatonin Levels and Sleep Quality.

Increased adenosine levels throughout the day promote sleepiness. A single nucleotide polymorphism (SNP) in the adenosine deaminase ADA gene (rs73598374) has been shown to affect sleep regulation. The extent to which lower ADA enzymatic activity is associated with the homeostatic sleep factor, melatonin, is uncertain. To test this possibility, we assessed the relationship between the ADA polymorphism and evening melatonin levels, as well as self-reported sleep behavior. Given the close relationship between mood and sleep behavior, we further tested the impact of ADA genotype on self-reported mood. We show that relative to the GG homozygotes, the A allele carriers (higher adenosine levels) had significantly higher evening melatonin levels as well as significantly better sleep quality. We further show the correlations between sleep and mood measures were altered by ADA genotype, with a stronger relationship observed in the GG (lower adenosine) group. Combined, these findings advance our understanding of the biochemistry of melatonin production by showing that there is a relationship between ADA genotype and melatonin levels. The differential relationships between sleep and psychological health between the genotype groups may reveal novel insights about the development of genotype-specific progression of various psychological disorders such as chronic anxiety and stress.

Minor allele of rs12976445 polymorphism in the promoter region of microRNA-125a is associated with the severity of primary open-angle glaucoma (POAG)

IntroductionThe signaling pathway of IL-6 has been reported to be associated with the severity of glaucoma. And the rs12976445 SNP in miR-125 could alter the expression of miR-125, which is directly targeted by IL-6R.Material and methodsIn this study, we recruited 88 POAG patients and grouped them according to their genotype of rs12976445 as GG group, GC group and CC group to study the association between the miR-125a polymorphism and POAG. We collected demographic characteristics and peripheral blood samples from 88 subjects. Then, rs12976445 genotypes in these subjects were determined to evaluate their relationship with the POAG index. THP-1 and U937 cells were transfected with miR-125a mimic or IL-6R siRNA to assess the relationship between miR-125a and IL-6R/ACHE.ResultsIL-6R is a downstream target of miR-125a and the overexpression of miR-125a showed significantly decreased mRNA and protein levels of IL-6R. The expression levels of miR-125a were the highest in the GG group and the lowest in the CC group, while the activity of IL-6 was comparable in the three groups. Moreover, the mRNA and protein levels of IL-6R were the lowest in the GG group and the highest in the CC group. Additionally, significantly thinner RNFL, larger average cup disc ratio, larger vertical cup disc ratio, and depressed visual field were observed in POAG patients carrying the CC genotype.ConclusionsIn summary, our data suggested that the rs12976445 polymorphism was significantly associated with the risk of POAG.

36344 Effect of CHRNA5 genetic variation and smoking on alcohol related phenotypes in healthy adult drinkers

ABSTRACT IMPACT: Understanding the influence of genetic variation and smoking on alcohol consumption helps in improving the treatment strategies for alcohol addiction OBJECTIVES/GOALS: Variation in the nicotinic receptor gene CHRNA5 (rs16969968) is associated with nicotine use and dependence, however its role in alcohol consumption is unclear. This study examined the effects of rs16969968 and smoking on alcohol related phenotypes in people without alcohol use disorder (AUD). METHODS/STUDY POPULATION: The study included 1,037 healthy adult drinkers without AUD (201 smokers, 836 non-smokers). A subset (n=161) participated in an Intravenous Alcohol Self-Administration (IV-ASA) laboratory session. Alcohol-related measures included Timeline Followback (TLFB), which measures drinking quantity and frequency in the past 90 days, and the Alcohol Use Disorders Identification Test (AUDIT), which measures alcohol use and consequences. IV-ASA measures included average and peak breath alcohol concentration (BrAC). The effect of rs16969968 was tested using a dominant model based on the presence of the A allele, and the influence of the rs16969968 polymorphism and smoking on alcohol phenotypes was assessed using t-tests and two-way ANOVA. RESULTS/ANTICIPATED RESULTS: There was a main effect of rs16969968 genotype with A-allele carriers (AA/AG) showing higher AUDIT-Dependence scores compared to the GG group. A main effect of smoking was observed on all the TLFB and AUDIT measures, with smokers showing greater alcohol consumption and problems compared to non-smokers. In the rs16969968 AA/AG group, smokers reported significantly more drinking days (p&lt;0.0001), and greater number of drinks (p&lt;0.0001), as well as higher AUDIT scores than non-smokers. IV-ASA measures did not show any difference between genotype groups or between smokers and non-smokers. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study identifies both independent and interactive effects of CHRNA5 gene variation and smoking on alcohol drinking measures and provides strong evidence for the effect of smoking on alcohol drinking and its consequences.

Influence of single nucleotide polymorphism of LAT1 on therapeutic response to gabapentinoids in Pakistani patients with neuropathic pain.

Gabapentinoids are substrate of L-type amino acid transporter 1 (LAT1) for distribution across the blood-brain barrier. The present study aimed to evaluate the effect of LAT1 rs4240803 genetic polymorphism on the clinical efficacy and tolerability of gabapentinoids in Pakistani patients with neuropathic pain. Three-hundred and ninety-two patients were recruited, genotyped for SNP rs4240803, and followed up for eight weeks to evaluate the clinical response to gabapentinoids in terms of pain relief, inadequate response, and the emergence of adverse events. LAT1 rs4240803 GG, GA, and AA genotype frequency were 33.42%, 47.96% and 18.62%, respectively. Out of 392 patients, 323 responded to the treatment and 17.6% discontinued either due to insufficient response or intolerable adverse events (AEs). GA genotype was more frequent in non-responder group (P˂0.001). Maximum pain responders (≥50%) in combination with the lowest incidence of AEs were observed in the GG group, whereas partial responders belonged to GA genotype and with the highest frequency of somnolence (83.6%) and dizziness (69.9%). Overall, 72.5% patients with GA genotype experienced AEs (P˂0.001). In conclusion, clinical outcomes of gabapentinoids are influenced by LAT1 rs4240803 polymorphism and population pharmacogenetics should be considered to evaluate the maximum potential of gabapentinoids in the management of neuropathic pain.

Impact of Potential Probiotic Lactobacillus Strains on Host Growth and Development in a Drosophila melanogaster Model.

Lactobacillus paracasei SD1, Lactobacillus rhamnosus SD11, and Lactobacillus gasseri SD12 were proposed as potential probiotics for oral health. However, the effects of them on host physiology are still unknown. This study aimed to select strains that can promote host growth and development in monocolonized Drosophila model compared with axenic and the commercial Lactobacillus rhamnosus GG-treated flies. The morphogenesis and growth of axenic Drosophila melanogaster were assessed from embryo to adult stage when provided with each probiotic strain-supplemented food. The colonization and persistence of probiotic in fly gut were also evaluated. The results indicated that axenic condition caused the lowest adult weight and emergence rate. All probiotic groups had higher weight than axenic group. Lact. rhamnosus SD11 group presented high adult emergence rate equivalent to Lact. rhamnosus GG group, which is significantly higher than the others. However, Lact. gasseri SD12 group had significantly lower adult weight and emergence rate when compared with Lact. rhamnosus GG group. The gut probiotics levels were rapidly increased within the first day after receiving probiotics. After probiotic cessation, their number in gut decreased and was maintained at low level, except for Lact. gasseri SD12, which completely vanished since day one. In conclusion, Lact. paracasei SD1, Lact. rhamnosus SD11, and Lact. rhamnosus GG can affect morphogenesis and weight of flies when fed since immature stage and have short period gut colonization. The findings of this study could possibly imply comparable health-promoting effects between Lact. paracasei SD1 and Lact. rhamnosus SD11 to commercial strain in Drosophila model.

The μ-opioid receptor gene polymorphism 118A>G weakens the pharmacological action of buprenorphine.

Opioids are commonly used analgesics for moderate to severe pain, but levels of drug effect vary among individuals. As for the mechanisms underlying these individual differences, there have been reports suggesting effects of polymorphisms in the gene encoding μ-opioid receptor (OPRM1). However, whether these polymorphisms affect the actions of μ-opioid receptor partial agonists has yet to be determined. This study aimed to assess differences in the pharmacological actions of buprenorphine, a μ-opioid receptor partial agonist, due to a polymorphism (A118G, rs1799971) in the OPRM1 gene in humans. Ten healthy adult men (5 with OPRM1 c.118AA and 5 with OPRM1 c.118GG) received a single intravenous dose of buprenorphine hydrochloride at 0.001 mg/kg. Blood samples were collected up to 360 minutes after drug administration to assess the pharmacokinetics of buprenorphine. Nociceptive thresholds (temperature), digital symbol substitution test (DSST), and visual analog self-rating scale (VAS) for subjective symptoms were also evaluated over time to assess the pharmacodynamics. Nociceptive thresholds were significantly increased in the AA as compared to the GG group after buprenorphine administration (p = 0.025), while the DSST scores were significantly lower in the AA group (p < 0.001). The VAS scores for drowsiness (p < 0.001), malaise (p < 0.001), nausea (p < 0.001), and euphoria (p = 0.004) were higher in the AA than in the GG group. Levels of pharmacological actions of a μ-opioid receptor partial agonist vary in accordance with a polymorphism in the OPRM1 gene (A118G).

A Low ω-6 to ω-3 PUFA Ratio (n–6:n–3 PUFA) Diet to Treat Fatty Liver Disease in Obese Youth

ABSTRACTBackgroundRecent literature suggests that the Western diet's imbalance between high ω-6 (n–6) and low ω-3 (n–3) PUFA intake contributes to fatty liver disease in obese youth.ObjectivesWe tested whether 12 wk of a low n–6:n–3 PUFA ratio (4:1) normocaloric diet mitigates fatty liver and whether the patatin-like containing domain phospholipase 3 (PNPLA3) rs738409 variant affects the response.MethodsIn a single-arm unblinded study, obese youth 9–19 y of age with nonalcoholic fatty liver disease were treated with a normocaloric low n–6:n–3 PUFA ratio diet for 12 wk. The primary outcome was change in hepatic fat fraction (HFF%), measured by abdominal MRI. Metabolic parameters included alanine aminotransferase (ALT), lipids, measures of insulin sensitivity, and plasma oxidized linoleic acid metabolites (OXLAMs). Outcomes were also analyzed by PNPLA3 rs738409 genotype. Wilcoxon's signed rank test, the Mann–Whitney U test, and covariance pattern modeling were used.ResultsTwenty obese adolescents (median age: 13.3 y; IQR: 10.5–16.4 y) were enrolled and 17 completed the study. After 12 wk of dietary intervention, HFF% decreased by 25.8% (P = 0.009) despite stable weight. We observed a 34.4% reduction in ALT (P = 0.001), 21.9% reduction in triglycerides (P = 0.046), 3.28% reduction in LDL cholesterol (P = 0.071), and a 26.3% improvement in whole body insulin sensitivity (P = 0.032). The OXLAMs 9-hydroxy-octadecandienoic acid (9-HODE) (P = 0.011), 13-HODE (P = 0.007), and 9-oxo-octadecadienoic acid (9-oxoODE) (P = 0.024) decreased after 12 wk. HFF% declined in both the not-at-risk (CC/CG) and at-risk (GG) PNPLA3 rs738409 genotype groups, with significant (P = 0.016) HFF% reduction in the GG group. Changes in 9-HODE (P = 0.023), 9-oxoODE (P = 0.009), and 13-oxoODE (P = 0.003) differed between the 2 genotype groups over time.ConclusionsThese data suggest that, independently of weight loss, a low n–6:n–3 PUFA diet ameliorates the metabolic phenotype of adolescents with fatty liver disease and that response to this diet is modulated by the PNPLA3 rs738409 genotype.This trial was registered at clinicaltrials.gov as NCT01556113.

Different subtypes of collateral vessels in hemorrhagic moyamoya disease with p.R4810K variant

BackgroundThe aim of this study was to investigate the hemorrhgic sites and collateral vessels in hemorrhagic MMD with the p.R4810K variant.MethodsHemorrhage sites were classified as either anterior or posterior. Collateral vessels were classified into three subtypes according to origin: lenticulostriate anastomosis, thalamic anastomosis, and choroidal anastomosis. Hemorrhage sites and collateral vessels were compared between patients with wild-type p.R4810K variant (GG) and patients with heterozygous p.R4810K variant (GA) after 1:1 propensity score matching.ResultsA total of 130 hemorrhagic MMD patients were included in present study, 21 pairs (42 hemorrhagic hemispheres) were obtained after 1:1 propensity score. In GA group, 16 hemispheres (76.2%) presented anterior hemorrhage, and 5 hemispheres (23.8%) presented with posterior hemorrhage. In GG group, 13 hemispheres (61.9%) presented anterior hemorrhage, and 8 hemispheres (38.1%) presented with posterior hemorrhage. No significant differences were found in hemorrhagic sites between two matched groups (P > 0.05). Of 21 hemispheres in GA group, 10 (47.6%) exhibited lenticulostriate anastomosis, 6 (28.6%) thalamic anastomosis, and 6 (28.6%) choroidal anastomosis. Of 21 hemispheres in GG group, 3 (14.3%) exhibited lenticulostriate anastomosis, 5 (23.8%) thalamic anastomosis, and 9 (42.9%) choroidal anastomosis. There was significant difference in lenticulostriate anastomosis between two matched groups (P = 0.045). After adjustment the age, sex, and PCA involvement, we found that lenticulostriate anastomosis was associated with p.R4810K variant (OR, 5.995; 95% CI, 1.296–27.737; P = 0.022).ConclusionLenticulostriate anastomosis might be associated with p.R4810K variant. Whereas hemorrhagic sites, thalamic anastomosis, and choroidal anastomosis might not be associted withp.R4810K variant.

The 2039 A/G FSH receptor gene polymorphism influences glucose metabolism in healthy men

ObjectiveTo assess the role of c. 2039 A/G (p. Asp680Ser) (rs6166) and c. −29 G/A (rs1394205) follicle-stimulating hormone receptor (FSHR) gene single nucleotide polymorphisms (SNPs) in a cohort of healthy men.MethodsOne-hundred twenty-seven healthy men underwent evaluation of the anthropometric parameters, assessment of metabolic and lipid profile, measurement FSH serum levels, and genotyping of both the aforementioned FSHR SNPs. Data grouped according to the FSHR rs6166 or rs1394205 genotypes underwent to statistical analysis.Main resultsThe three groups of men for each FSHR SNP did not differ statistically significantly for body mass index and serum FSH levels. As for FSHR rs6166 SNP, glucose levels were significantly lower in men with the GG genotype compared with those with the AA genotype. Men with AG had lower insulin levels and HOMA index values compared with those carrying the genotype AA (p < 0.05). The GG group showed a negative correlation between serum FSH levels and insulin and between serum FSH levels and HOMA index (p < 0.05). In contrast, men grouped according to the FSHR rs1394205 genotype showed no significant difference in blood glucose, serum insulin levels, and HOMA index. The AG group showed a negative correlation between FSH insulin and between serum FSH levels and HOMA index (p < 0.05).ConclusionsMen with the genotype GG of the FSHR rs6166 SNP have lower blood glucose levels than those with the AA genotype. Their FSH levels inversely correlated with insulin and HOMA index. In contrast, the genotype FSHR rs6166 A/G did not reveal any role of FSH on glucose metabolism in healthy men. The inverse relationship between FSH and insulin or HOMA index in the group with the genotype GG of the FSHR rs6166 SNP suggests a possible cross-talk between FSH and insulin.

Relationship between interleukin-13 rs20541 single nucleotide polymorphisms and therapeutic efficacy in children with asthma.

ObjectiveTo investigate the relationship between therapeutic efficacy in children with asthma and interleukin-13 (IL-13) rs20541 polymorphisms.MethodsFifty children with moderate-to-severe asthma were assigned to the GG, GA, and AA groups according to the IL-13 gene locus rs20541 polymorphism. The patients received budesonide inhalation suspension 1 mg twice daily combined with fluticasone propionate 80 µg/inhalation. The improvement of clinical symptoms (gasping, coughing, and wheezing), improvement of lung function, and adverse reactions were observed.ResultsLung function did not significantly differ among three groups before treatment. After treatment, the time to symptom relief was significantly shorter in the GG group than that in the other two groups. The forced expiratory volume in one second and percent predicted peak expiratory flow were also significantly better in the GG group than in the other two groups.ConclusionBudesonide inhalation suspension combined with fluticasone propionate is an effective treatment regimen for moderate-to-severe asthma. Polymorphism of the IL-13 rs20541 locus may be correlated with therapeutic efficacy. Patients carrying the GG allele were more responsive than their counterparts with the GA or AA allele.

AB0173 ALLELIC POLYMORPHISM OF PROINFLAMMATORY CYTOKINE GENES AS A BASIS FOR THE FORMATION OF PHENOTYPES OF JUVENILE IDIOPATHIC ARTHRITIS

Background:The pathological process of juvenile idiopathic arthritis (JIA) largely depends on pro-inflammatory cytokines, the polymorphism of the alleles of some genes of which we have the opportunity to study. No studies have been conducted on the dependence of certain features of the pathological process of JIA on the polymorphism of the IL-6(G-174C) and TNF(G308A) genes.Objectives:To reveal the dependence of JIA phenotypes and its course on genetic polymorphism of alleles IL-6 and TNF.Methods:Polymorphism of the IL-6 and TNF genes was studied by PCR-method using allele-specific primers 44 patients 1-17 y.o. (24f, 20m) with JIA. The level of IL-6 and TNFα in the serum was determined using ECLIA and CLIA methods.Results:There were 73% cases with an unfavorable course of the disease (UCD) of the patients with the CC allele of the IL-6 gene, for most patients average activity was JADAS27 13.5±1.6. oJIA (50%) &amp; uveitis (30%) were the most frequent among subgroups. The level of serum IL6 was 74.1±69.5 pg/ml, TNFα 27.4±17.3 pg/ml (ratio IL6/TNFα=4.3±2.1). Among patients with GC IL6 70% female, 79% with UCD. More often pJIA (36%, including all RF+) and eJIA (35%) were noted with the largest frequency of inclusion of the hip joints (33%), spine (35%), detection of secondary osteoporosis (43%). The metabolic changes were registered on the ECG in 82% cases. The serum IL-6 level was 11.35±2.95 pg/ml, TNF 241.75 pg/ml (IL-6/TNFα=0.047, p&lt;0.05 vs CC allele). Children with GG IL-6 (wild allele) with a more favorable course of the JIA (31%, less than in the CC and GC groups (p&lt;0.05), only 8% had the highest disease activity), the largest number of patients with sJIA (25%) was registered in this group. The detection of HLA B27 was significantly lower (p&lt;0.05) than in other alleles, while 60% cases were ANA+ (more than in the group GC, p&lt;0.05). The highest level of serum IL6 (35.3±18.9 pg/ml) &amp; the highest average number of mutations in folate metabolism genes (4±0.51) were revealed in this group. The wild allele GG prevailed (n=32) among the TNF gene alleles, sex ratio 1:1, UCD in 70%. The number of active joints, ESR, CRP, ANA-positivity (50%), HLA B27+ (53%) were unsignificantly higher than in GA TNF allele, while serum IL6 level (22.8±9.8 pg/ml) &amp; TNFα (12.3±4.1 pg/ml) were lower. In patients with the GA TNF gene allele, an UCD (73%), eJIA (36%) were noted slightly more often. By such parameters as the patient’s gender, the presence of uveitis, damage to the hip joints, the type of synovitis, metabolic changes on the ECG, indicators were observed comparable with the wild allele group. IL6 level was 48.3±39.2 pg/ml, TNFα 636.5±420.1 pg/ml, IL6/TNFα=0.07±0.06 (vs 1.9±0.5 in GG group, p&lt;0.05). The genotype of two wild alleles TNF GG with IL6 GG expectedly showed the smallest proportion of the UCD (33%, p &lt;0.05), the most frequency of ANA-positivity (71%), with no uveitis and RF+pJIA in this group. All cases of RF+pJIA had TNF GA and IL6 GC. oJIA prevailed (57%) in the TNF GG&amp;IL6 CC group, there was not a single case of sJIA, and the AJ number was the smallest (2.86±0,5). The largest group was TNF GG &amp; IL6 GC (n=14). 91% of cases had UCD, AJ=6.6±2.4, damage to the hip joints in 40%, ESR 23.7±6.7 mm/h, CRP 14.5±5.4 mg/l, metabolic changes on the ECG in 100%, but ANA+ only at 13%. In general, there was no correlation between the cytokine content in the blood serum during of active disease in the examined children with features of allelic polymorphism of these genes.Conclusion:Depending on the allele polymorphism of the IL-6 and TNF genes, certain phenotypes of the JIA course may be distinguished. Thus, revealing the polymorphism of these alleles in patients at the onset of the disease, we can predict to some extent its course and take this into account when choosing treatment tactics.Disclosure of Interests:None declared

Supplementation of Geranylgeraniol and Tocotrienols to High-Fat Diet Shifts the Gut Microbiome Composition and Function in Type 2 Diabetic Mice

Abstract Objectives In recent years, characterization of gut microbiota composition and function were linked to the progression of type 2 diabetes mellitus. Recent evidence showed that Geranylgeraniol, an isoprenoid found in fruits, vegetables, and grains, improves glucose homeostasis. Similarly, Tocotrienols, a subfamily of vitamin E, also contains anti-diabetic properties. In this study, we examined the combined effect of geranylgeraniol and tocotrienols on the composition and function of gut microbiome in obese male mice. Methods Forty male C57BL/6J mice were assigned to 4 groups in a factorial design as follows: high-fat diet (HFD) (control group), HFD + geranylgeraniol [400 mg/kg diet] (GG group), HFD + tocotrienols [400 mg/kg diet] (TT group), and HFD + geranylgeraniol + tocotrienols (G + T group) for 14 weeks. 16S rRNA gene sequencing was done from cecal samples and microbiome and data analysis was performed with QIIME2 and PICRUSt2. Results Across all groups, the most abundant phyla were Verrucomicrobia, Firmicutes, Bacteroidetes, and Actinobacteria. There was no difference in alpha diversity among different groups. Different treatments influenced the relative abundance of certain bacteria. In the Bacteroidetes phylum, the relative abundance of family S24–7 increased in the TT group only. In the Firmicutes phylum, the relative abundance of family Lachnospiraceae was reduced upon the supplementation of geranylgeraniol or tocotrienols; individually or in combination. In Verrucomicrobia phylum, Akkermansia muciniphila relative abundance was reduced in the TT group but increased in the G + T group. The results of functional profiling of the gut microbiome revealed that geranylgeraniol supplementation caused an increase in the proportion of biosynthetic pathways related to purine, pyrimidine, and inosine-5’-phosphate and hexitol fermentation, and a decrease in the proportion of pathways involved in the biosynthesis of isoleucine, valine, histidine, arginine, and chorismate. The G + T group increased pathways related to thiamine diphosphate biosynthesis, and decreased others involved into sulfur oxidation and methylerythritol phosphate. Conclusions The influence of geranylgeraniol and tocotrienols supplementation on gut microbiome composition and function, suggests a prebiotic potential for the potential of geranylgeraniol and tocotrienols. Funding Sources American River Nutrition, LLC, Hadley, MA.

Angiographic characteristics in Moyamoya disease with the p.R4810K variant: a propensity score‐matched analysis

The p.R4810K variant was identified as a strong susceptibility in patients with Moyamoya disease (MMD). The aim of this study was to investigate the angiographic characteristics in MMD with the p.R4810K variant. Angiographic characteristics were compared between patients with wild-type p.R4810K variant (GG) and patients with heterozygous p.R4810K variant (GA) after 1:1 propensity score matching, including Suzuki stage, collateral circulation and external carotid artery (ECA) collateral. Collateral circulation was graded with scores ranging from 0 to 12: posterior collateral circulation from the posterior cerebral artery to the middle cerebral artery and anterior cerebral artery was scored from 0 to 6; anterior collateral circulation was scored as 6 to 0 corresponding to Suzuki stages 0 to 6. A total of 489 patients were screened; 133 pairs were obtained after 1:1 propensity score matching. Compared with the patients in the GA group, unilateral MMD was more frequent in the GG group (P=0.026). Hemispheres in the GA group (86/266) had more posterior cerebral artery involvement than hemispheres in the GG group (48/266) (P<0.001). Hemispheres in the GA group had a lower grade in collateral circulation than hemispheres in the GG group (P=0.011), but ECA collateral was more frequently observed in the GA group than in the GG group (53.4% vs. 39.8%, P=0.002). Superficial temporal artery and occipital artery collateral was more frequently observed in the GA group than in the GG group (P<0.05). Patients in the GA group had lower grades in collateral circulation than patients in the GG group, but ECA collateral was more frequently observed in the GA group than in the GG group.