GNB3 Polymorphism Research Articles

Endothelium function biomarkers and carotid intima-media thickness changes in relation to NOS3 (rs2070744) and GNB3 (rs5443) genes polymorphism in the essential arterial hypertension.

Objective. The aim of the present study was to clarify the endothelial function biomarkers and carotid "intima media" thickness (IMT) changes in relation to GNB3 (rs5443) and NOS3 (rs2070744) genes polymorphism in the essential arterial hypertension (EAH). Methods. One-hundred EAH patients (48 - control) participated in the case-control study. Soluble vascular cell adhesion molecule (sVCAM-1), total NO metabolites (NO2 -+NO3 -), transcriptional activity of NOS3 gene, endothelium-dependent flow-mediated dilation of the brachial artery (FMD BA), and carotid IMT were studied. GNB3 (rs5443) and NOS3 (rs2070744) genotyping was performed by TaqMan probes (CFX96™Real-Time PCR). Results. The connection of NOS3 (rs2070744) with decreased total NO metabolites (F=71.11; p<0.001), reduced NOS3 genes transcription activity (F=8.71; p<0.001) and increased sVCAM-1 (F=6.96; p=0.002), especially in the C-allele carriers (particularly in CC-genotype patients with lower NO - 16.46% and 40.88%; p<0.001), lowered the transcription activity of NOS3 gene - 46.03% 7 times (p<0.001), and become higher sVCAM-1 - 35.48% and 89.48% (p<0.001), respectively. ANOVA did not confirm the association of GNB3 (rs5443) gene with endothelial function and carotid IMT. Severe EAH was associated with increased carotid IMT - 50.0% (p<0.001) and 57.14% (p=0.007), wider carotid arteries - 17.36% (p=0.012) and 21.79% (p=0.004), and decreased NOS3 genes transcription activity - 34.54% (p=0.003). Atherosclerotic plaques were unilateral - 24.77% (χ2=5.35; p=0.021) or bilateral - 27.62% (χ2=5.79; p=0.016). IMT---gt---0.9 mm was followed by a higher BP (p<0.001), FMD BA 11.80% decrease with compensatory increase in carotid arteries diameters - 17.38% and 21.99% (p<0.001) and sVCAM-1 by 20.49% (p=0.005). Conclusion. NOS3 (rs2070744), but not GNB3 (rs5443), gene associated with the essential arterial hypertension severity relying upon the endothelial function impairment and NOS3 genes reduced transcription activity.

The contribution of the AGT, GNB3, MTHFR, MTRR, ApoE, and PPARα polymorphisms to the development of masked arterial hypertension in patients with low and moderate cardiovascular risk

Aim: To assess the probability of masked arterial hypertension (MAH) in patients with low and moderate cardiovascular risk depending on polymorphisms in selected genes.Materials and methods: Ninety two (92) patients (mean age, 41.93±8.92 years) with low and moderate cardiovascular risk without any documented cardiovascular disorders were assessed clinically and had 24-hour ECG monitoring performed, as well as genotyping on the following markers: AGT Thr174Met rs4762, GNB3 C825T rs5443, MTHFR C677T rs1801133, MTRR Ile22Met rs1801394, ApoE Cys130Arg rs 429358, and PPARα G/C rs4253778. Depending on the presence of MAH, the patients were divided into two groups: with newly diagnosed arterial hypertension corresponding to the MAH criteria (n=58, 63%) and with normal office-based and ambulatory blood pressure and normal blood pressure according to the results of 24-hour ECG monitoring (n=34, 37%).Results: Two groups were not different by their age, cardiovascular risk factors, concomitant diseases and clinical characteristics. There were more men than women in the MAH group (р=0.028). In MAH patients, the most prevalent was Ile22Met rs1801394 A/G polymorphism of the MTRR gene (the odds ratio (OR) and relative risk (RR) for MAH were 4.23 [95% сonfidence interval (CI) 1.56–11.72] and 2.17 [1.25–4.12], respectively). The Cys130Arg rs 429358 Т/С genotype polymorphism of the АроЕ gene was also significant. The probability of MAH in the patients with АроЕ Т/С genotype was more than 3-fold higher: OR 3.67 [95% CI 1.34–10.28], RR 2.15 [95% CI 1.17–4.36]. The correlation analysis showed a moderate association between MAH and MTRR and АроЕ gene polymorphisms (Q=0.62 and Q=0.57, respectively).Conclusion: In patients with low and moderate cardiovascular risk, the probability of MAH depends not only from their gender, but also from their genetic background. The candidate genes for MAH in such patients are Ile22Met rs1801394 A/G polymorphism of the MTRR gene and Cys130Arg rs 429358 Т/С polymorphism of the АроЕ gene.

INTERCONNECTION BETWEEN TUBULAR RENAL DYSFUNCTION AND GENES POLYMORPHISM IN PATIENTS WITH ARTERIAL HYPERTENSION

Objective: Objective: to assess the relationship between NGAL concentration as an indicator of tubular disorders, and genetic markers of cardiovascular risk in hypertensive patients. Design and method: Materials and methods: 89 patients of working age with hypertension (mean age 48.32 ± 8.71) were examined, who were divided into 2 groups depending on serum NGAL. Group 1 - 20 patients with NGAL levels above reference values, Group 2 - 69 patients with NGAL levels in the range of normal values. For all patients, to evaluate tubular renal function, the concentration of NGAL in serum was determined by ELISA. All patients were examined for genotypes of AGT Thr174Met, GNB3 C825T, MTHFR C677T, MTRR Ile22Met, ApoE Cys130Arg, PRARA rs4253778. Results: Results: patients in the groups did not significantly differ in age, gender, risk factors, concomitant diseases and therapy, blood pressure and lipid profile. In group 1, the occurrence of AGT, MTHFR, and PRARA gene polymorphism was significantly higher in heterozygous form than in group 2 (p = 0.002, p &lt; 0.001, and p = 0.037, respectively). Patients in the groups did not significantly differ in occurrence of GNB3, MTRR, and ApoE gene polymorphism. Correlation analysis showed a direct relationship between the concentration of NGAL in the blood and the presence of AGT gene polymorphism (r = 0.38; p &lt; 0.05), GNB3 (r = 0.33; p &lt; 0.05), MTHFR (r = 0.35; p &lt; 0.05). The association of NGAL with the polymorphism of the GNB3, MTRR, and ApoE genes was not statistically significant. Conclusions: Conclusions: in patients of working age with hypertension, tubular dysfunction, assessed by the concentration of NGAL in the blood, is associated with the presence of AGT, MTHFR, PRARA gene polymorphism in a heterozygous form.

Relationship of gene polymorphism with the nature of target organ damage in patients with arterial hypertension

Objective: to assess the relationship of polymorphism of the main genes involved in the pathogenesis of arterial hypertension (AH) with indicators reflecting the state of target organs in the group of patients with arterial hypertension.Material and methods: we examined 100 patients with arterial hypertension who underwent standard diagnostic procedures, as well as molecular genetic research.Results: in patients with arterial hypertension statistically significant associations of AGTR2, GNB3, and NOS3 gene polymorphism with left ventricular hypertrophy, CYP11B2 and NOS3 gene polymorphism with left ventricular diastolic dysfunction, and NOS3 gene polymorphism with increased vascular wall stiffness were found (p &lt; 0.05).Conclusions: the results of the study indicate that patients with arterial hypertension are a genetically heterogeneous group in terms of the relationship of specific gene polymorphism with indicators that characterize the state of target organs. The use of genetic approaches is promising for early screening of patients with arterial hypertension, belonging to the high-risk group, in order to ensure timely and effective organoprotection.

Analysis of HCRTR2, GNB3, and ADH4 Gene Polymorphisms in a Southeastern European Caucasian Cluster Headache Population.

Studies point to an increased hereditary risk of cluster headache. HCRTR2 gene rs2653349 and ADH4 gene rs1800759 polymorphisms have been associated with cluster headache susceptibility. Also, GNB3 rs5443 polymorphism, associated with increased signal transduction via GPCRs, seems to influence triptan treatment response. DNA from 114 cluster headache patients and 570 non-related controls, representing a general Southeastern European Caucasian (SEC) population, was extracted from buccal swabs and genotyped using real-time PCR. Gene distribution for the rs2653349 was GG = 79.8%, GA = 18.4%, and AA = 1.8% for patients and GG = 79.1%, GA = 19.1%, and AA = 1.8% for controls. The frequency of the mutated A allele was 11.0% for patients and 11.3% for controls. The frequencies for rs5443 were CC = 44.7%, CT = 44.7%, and TT = 10.5% for patients and CC = 43.9%, CT = 42.6%, and TT = 13.5% for controls. The frequency of the mutated T allele was 32.9% for patients and 34.8% for controls. A 2.7-fold more frequent appearance of the mutated T allele was observed in patients with better triptan treatment response, although not statistically significant. For rs1800759, the frequencies were CC = 36.0%, CA = 43.0%, and AA = 21.0% for patients and CC = 34.0%, CA = 50.2%, and AA = 15.8% for controls. The frequency of the mutated A allele was 42.5% and 40.9% for patients and controls, respectively. The mutated T allele of GNB3 rs5443 polymorphism was more prevalent in patients with better triptan treatment response, indicating a possible trend of association between this polymorphism and triptan treatment response in SEC population. According to our observation, no association of HCRTR2 rs2653349 and ADH4 rs1800759 polymorphisms and cluster headache in SEC population could be documented.

P3571Genes polymorphism and renal dysfunction formation in arterial hypertension patients with high adherence to treatment

Abstract Objective To evaluate the contribution of gene polymorphism to the formation of renal dysfunction in patients with hypertension with high adherence to treatment. Methods and materials 88 working-aged subjects with non-complicated arterial hypertension (average age 48,65±7,24 yrs). All patients underwent evaluation of genotype for markers AGT Thr174Met, GNB3 C825T, MTHFR C677T, MTRR Ile22Met. To assess the glomerular function, cystatin C was measured in serum by ELISA, and serum level of NGAL was determined by ELISA to assess the function of the tubules.Depending on genotype peculiarities the following groups were formed: 1) 39 patients who had polymorphism of AGT Thr174Met in homozygous and 49 subjects without one; 2) 62 subjects who had polymorphism of GNB3 C825T in heterozygous and 26 subjects without one; 3) 52 subjects with polymorphism of MTHFR C677T in heterozygous and 36 subjects without one; 4) 48 subjects with polymorphism of MTRR Ile22Met in heterozygous and 40 subjects without one. Results Patients in the groups did not differ in sex, age, risk factors, comorbidities, concomitant medications, BP level, lipid spectrum. In the groups with the presence of the genes GNB3 and MTHFR polymorphism in the heterozygous form, the level of NGAL was significantly higher than in the groups with normal genotypes: 1.67±0.86 ng/ml versus 1.2±0.87 pg/ml (p=0.022), 1.49±0.61 pg/ml versus 1.21±0.56 ng/ml (p=0.034), respectively. At the same time, in these groups, the level of cystatin C was not significantly different. The AGT gene polymorphism groups differed significantly in cystatin C (p&lt;0.001), but did not differ in the level of NGAL. In the group with the presence of the MTRR gene polymorphism, the level of cystatin C and the level of NGAL were significantly higher (p=0.042 and p=0.004, respectively). The correlation analysis revealed a moderate direct interconnections between cystatin C levels and the presence of the AGT gene polymorphism (r=0.46; p=0.017) and MTRR (r=0.33; p=0.039), as well as between the NGAL level and the presence of the GNB3 gene polymorphism (r=0.42; p=0.031), MTHFR (r=0.39; p=0.023) and MTRR (r=0.43; p=0.007). Conclusions In working-aged patients with uncomplicated hypertension with high adherence to treatment, the formation of renal dysfunction with a primary glomerular lesion is associated with the presence of polymorphism of the AGT gene in the heterozygous form. Formation of renal dysfunction with predominant tubular lesion is associated with the presence of GBN3 and MTHFR genes polymorphism of in the heterozygous form. And the formation of renal dysfunction with the damage of both glomeruli and tubules is associated with the presence of the MTRR gene polymorphism of the in the heterozygous form.

Gene Polymorphisms and Susceptibility to Functional Dyspepsia: A Systematic Review and Meta-Analysis.

Functional dyspepsia (FD) is a common chronic gastrointestinal disorder with a complex, undefined mechanism. Clustering of patients with FD in families highlights the role of genetic factors in the pathogenesis of FD. We performed a systematic review and meta-analysis to clarify the associations between specific gene polymorphisms and FD susceptibility. PubMed, EMBASE, the Cochrane Library, and HuGE database were searched. An additive model was adopted to determine whether previous studied genes are associated with FD susceptibility. Carriers of minor allele in GNB3 825C>T (OR = 1.15, 95% CI 0.99-1.34, P = 0.07), SCL6A4 5HTTLPR (OR = 0.92, 95% CI 0.75-1.12, P = 0.40), and CCK-1R 779T>C (OR = 0.86, 95% CI 0.72-1.03, P = 0.09) genes failed to demonstrate susceptibility to FD. In a subgroup analysis, only minor allele (T) in GNB3 825C>T was associated with an increased susceptibility to the epigastric pain syndrome subtype (OR = 1.34, 95% CI 1.10-1.63, P = 0.003). Our meta-analysis based on available studies using an additive model failed to show that GNB3, SCL6A4, and CCK-1R polymorphisms are associated with FD susceptibility.

Association of SDF1β (G801A) and GNB3 (C825T) polymorphisms with the incidence and severity of coronary artery disease

Coronary artery disease (CAD), manifesting as angina and myocardial infarction, is a common cause of death and disability worldwide. In addition to major aetiologic determinants such as lifestyle a...

Comprehensive insight into functional interaction between GNB3 C825T and eNOS T‐786C, G894T gene polymorphisms and association with susceptibility to diabetic erectile dysfunction

No study has assessed the possible involvementof endothelial nitric oxide synthase (eNOS) T-786C and G894T and G-protein β3 subunit (GNB3) C825T polymorphisms with susceptibility to diabetic vasculogenic erectile dysfunction (VED) in North African subjects. Our aim was to evaluate the interaction and association between these gene polymorphisms and this disorder. A total of 164 type 2 diabetes patients with VED diagnosed with penile color Doppler ultrasonography and 148 age-matched healthy volunteers were genotyped for the rs1799983 (G894T) and rs2070744 (T-786C) of the eNOS gene and the rs5443 (C825T) of the GNB3 gene using the PCR-RFLP method. A significant association of the eNOS G894T (p=0.005) and T-786C (p=0.02) with altered susceptibility to VED was observed. The risk also holds for the G894T and T-786C eNOS gene polymorphisms when excluding patients with dyslipidemia and cardiovascular diseases (p=1.7·10-4 and p=3.2·10-5 , respectively). The univariate odds ratio associated with CC alleles of the eNOS T-786C revealed a four times increased risk for VED (OR=4.04; 95% CI=1.53-10.67;p=0.006). VED risk was also associated with the G894T variant under dominant model (p=0.002) and the T-786C variant under recessive model (p=0.004). Furthermore, the concomitant presence of the combined genotypes of the 894T and 786T strongly affected the predisposition to VED (p=0.007). Our study gave a comprehensive insight into functional interaction between GNB3 and eNOS gene polymorphisms and suggests that the eNOS G894T and T-786C variants are strong predisposing factors of VED susceptibility within men with type 2 diabetes.

Interactions of Genes and Sodium Intake on the Development of Hypertension: A Cohort-Based Case-Control Study.

There have been few studies investigating interactions of G-protein beta3 subunit (GNB3) C825T (rs5443) and dietary sodium intake on the risk of hypertension, i.e., BP salt sensitivity. The study aims to evaluate joint effects of GNB3 polymorphisms and sodium consumption on the development of hypertension. A cohort-based case-control study was conducted in 2014. There are 233 participants with newly diagnosed hypertension in the case group and 699 participants in the gender-matched control group. The primary outcome is the development of hypertension over a 10-year period. The determinants of hypertension were three genotypes of SNP in GNB3 (TT; CT; and CC) and two dietary salt categories on the basis of the level of sodium consumption representing high (>4800 mg/day) and low-sodium (<2400 mg/day) diets. The development of hypertension increased with participants carrying TT genotype and high-sodium diets comparing with those carrying TC or CC genotype with low-sodium diets (adjusted OR 3.23, 95% CI 1.52–6.83) (Rothman synergy index = 3.79). The study suggests that GNB3 C825T polymorphism may influence the response of the renin-angiotensin system to high-sodium diet. It implies that GNB3 can be served as an easy, inexpensive, and early genetic marker of salt sensitivity to blood pressure. Salt-sensitive individuals should pay more attention to salt intake to reduce cardiovascular morbidity or mortality.

Analysis of SNPs of MC4R, GNB3 and FTO gene polymorphism in obese Saudi subjects.

The goal of this study was to analyze the association between the FTO rs17817449 (G>T), G protein beta3 subunit (GNB3) C825T and Melanocortin 4 receptor (MC4R) A822G single nucleotide polymorphism (SNP) with obesity in Saudi subjects. The subjects were divided into 2 groups according to BMI: Obese (BMI> 29.9) and non- obese control (BMI<24.9). Genotyping of the target genes were determined by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism analysis (RFLP). We demonstrated the association of the FTO genotype TT with increased weight, BMI and leptin levels in both males and females. However, there was no association of genotype TT with fasting blood glucose, triglycerides and cholesterol levels. Regarding GNB3 rs5443 polymorphism, the likelihood of obesity was linked to the TT genotype which was also associated with increased leptin levels. On the other hand, the SNP of MC4R A822G did not exhibit any significant association with obesity among studied subjects and showed only the presence of homozygous AA genotype. The polymorphism of FTO gene rs17817449 and GNB3 gene rs5443 (C825T) may be a genetic determinant of obesity in Saudi population whereas impact of MC4R Asn274Ser change could not be detected.

Mutation in the beta3 subunit of Guanine nucleotide-binding protein (GNB3) gene is not associated with Type II diabetes mellitus risk: a case–control study of a North Indian population

Context: Genetics play a major role in development and pathophysiology of Type 2 diabetes mellitus (T2DM).Objective: To asses the association of Guanine nucleotide-binding protein (GNB3) (C825T) gene's polymorphism with T2DM.Materials and methods: A case–control study including 400 North Indians was performed using Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP) approach to analyze genetic polymorphism.Results: No significant difference was observed in genotype and allele frequencies of GNB3 gene on comparing cases with controls.Discussion: Our study is in agreement with studies on Polish, Japanese, Hispanic-American and Danish populations who observed no significant association between GNB3 (C825T) polymorphism and T2DM.Conclusion: GNB3 (C825T) polymorphism is not associated with T2DM.

GNB3 and CREB1 gene polymorphisms combined with negative life events increase susceptibility to major depression in a Chinese Han population.

BackgroundMajor depression (MD) is caused by a combination of genetic and environmental factors. In this study we investigated the interaction of variations in the G-protein beta 3 subunit (GNB3) and cAMP response element binding protein 1 (CREB1) genes with negative life events in the pathogenesis of MD. One GNB3 polymorphism (rs5443) and four CREB1 polymorphisms (rs2253206, rs2551941, rs6740584, rs11904814) were investigated based on known associations with MD.Methods512 patients with MD and 513 control subjects were genotyped. The frequency and severity of negative life events were measured by the Life Events Scale (LES). Gene-environment interactions (G×E) were assessed using the generalized multifactor dimensionality reduction (GMDR) method.ResultsDifferences in GNB3 rs5443 allele frequencies and genotype distributions were observed between MD patients and controls. Significant G×E interactions were detected between negative life events and genotypic variation of all five single nucleotide polymorphisms (SNPs). Individuals carrying the T- allele of rs5443 (CC), A- allele of rs2253206 (GG), T- allele of rs2551941 (AA), C- allele of rs6740584 (TT) or G- allele of rs11904814 (TT) conferred susceptibility to MD in subjects only exposed to high-negative life events. However, individuals with the T+ allele of rs5443 (CT, TT) were susceptible to MD when exposed to low negative life events.ConclusionsInteractions between GNB3, CREB1 and negative life events were revealed. Further evidence is provided about the role of the environment in genetic vulnerability to MD.

Association between single nucleotide polymorphisms in ADRB2, GNB3 and GSTP1 genes and high-altitude pulmonary edema (HAPE) in the Chinese Han population.

High altitude pulmonary edema (HAPE) occurs mainly under conditions such as high altitude, rapid ascent, or hypoxia. Previous studies suggest that ADRB2, GNB3, TH, and GSTP1 polymorphisms are associated with various lung diseases. We evaluated whether those polymorphisms are associated with the risk of HAPE in a Chinese Han population. ADRB2, GNB3, TH and GSTP1 polymorphisms were genotyped using a Sequenom MassARRAY. Logistic regression, adjusted for age and gender, was used to evaluate the association between the genotypes and the risk of HAPE by computing odds ratios (ORs) and 95% confidence intervals (95% CIs). The results revealed that GNB3 rs4963516 allele ‘‘G’’ (G vs T: OR = 0.70, 95% CI = 0.55–0.90, p = 0.006) was associated with HAPE risk. The ADRB2 rs1042718 alleles had a 1.29-fold (95%CI = 1.00-1.66; p = 0.045) increased risk of HAPE, and the GSTP1 rs749174 alleles had a 0.71-fold (95%CI = 0.52-0.99; p = 0.042) decreased risk of HAPE. Co-dominant and dominant models of GNB3 rs4963516 decreased the risk of HAPE (p = 0.023 and p = 0.008, respectively). Our results indicate GNB3 and GSTP1 polymorphisms may protect against HAPE progression, while ADRB2 polymorphisms are associated with an increased risk of HAPE.

Estimation of the relationship between the polymorphisms of selected genes: ACE, AGTR1, TGF\u03b21 and GNB3 with the occurrence of primary vesicoureteral reflux

PurposeEtiopathogenesis of VUR is composite and not fully understood. Many data indicate the importance of genetic predisposition. The aim of this study was to establish the relationship of selected polymorphisms: 14094 polymorphism of the ACE, polymorphism rs1800469 of TGFβ-1, rs5443 gene polymorphism of the GNB3 and receptor gene polymorphism rs5186 type 1 AGTR1 with the occurrence of the primary vesicoureteral reflux.MaterialThe study included 190 children: 90 with the primary VUR confirmed with the voiding cystourethrogram and excluded secondary VUR and a control group of 100 children without a history of the diseases of the genitourinary tract.MethodsThe study was planned in the scheme: “tested case versus control.” Genomic DNA was isolated from the leukocytes of peripheral blood samples. The results were statistically analyzed in the Statistica 10 using χ2 test and analysis of the variance Anova.ResultsAny of the four studied polymorphisms showed no difference in the distribution of genotypes between patients with primary vesicoureteral reflux and the control group. In patients with VUR and TT genotype polymorphism rs5443 GNB3 gene, the glomerular filtration rate was significantly higher than in patients with genotype CC or CT.Conclusions(1) No relationship was found between the studied polymorphisms (14094 ACE gene, rs1800469 gene TGFβ1, GNB3 gene rs5443, rs5186 AGTR1 gene) and the occurrence of primary vesicoureteral reflux. (2) TT genotype polymorphism rs5443 GNB3 gene may be a protective factor for the improved renal function in patients with primary vesicoureteral reflux in patients with genotype CC or CT.

Association of CLOCK, ARNTL, PER2, and GNB3 polymorphisms with diurnal preference in a Korean population

ABSTRACTPolymorphisms in human circadian genes are potential genetic markers that affect diurnal preference in several populations. In this study, we evaluated whether four polymorphisms in circadian genes CLOCK, ARNTL, PER2, and GNB3 were associated with diurnal preference in a Korean population. In all, 499 healthy subjects were genotyped for four functional polymorphisms in CLOCK, ARNTL, PER2, and GNB3. Composite scale of morningness (CSM) was applied to measure phenotype patterns of human diurnal preference. In addition, three subscale scores, i.e. “morningness,” “activity planning,” and “morning alertness,” were extracted from the CSM. No significant associations were observed between CSM scores and CLOCK (rs1801260) genotype or T allele carrier status, CSM scores and ARNTL (rs2278749) C allele carrier status, and CSM scores and GNB3 (rs5443) genotype or C allele carrier status. However, total CSM scores and scores of its subscales were significantly associated with PER2 (rs934945) genotype (p = 0.010, p = 0.018, and p = 0.005 for total, morningness, and activity planning, respectively) and G allele carrier status (p = 0.003, p = 0.005, and p = 0.002 for total, morningness, and activity planning, respectively). The best model result obtained by performing multifactor dimensionality reduction analysis (2 = 11.2798, p = 0.0008) indicated that interaction among C/T single nucleotide polymorphism (SNP) in ARNTL, C/T SNP in GNB3, and G/A SNP in PER2 synergistically affected the risk associated with diurnal preference toward eveningness. These results suggest that circadian gene PER2 is associated with diurnal preference in healthy Korean population. Although polymorphisms in ARNTL and GNB3 were not significantly associated with diurnal preference, their interactions with the polymorphism in PER2 may synergistically increase the risk of diurnal preference toward eveningness.

Functional dyspepsia susceptibility is related to CD14, GNB3, MIF, and TRPV1 gene polymorphisms in the Greek population.

Functional dyspepsia (FD) susceptibility might be influenced by polymorphisms of genes related to inflammation (CD14, macrophage migration inhibitory factor [MIF]), motor (GNB3), and sensory dysfunction (GNB3, TRPV1). We examined the association between CD14 rs2569190, GNB3 rs5443, MIF rs222747, and TRPV1 rs755622 gene polymorphisms with FD (Rome III criteria) in the Greek population. We genotyped 174 dyspeptics (115 with epigastric pain syndrome; 41% Helicobacter pylori positive) and 181 controls using polymerase chain reaction-based methods and we measured disease symptoms' burden with a modified Gastrointestinal Symptoms Related Scale. Homozygous for the TT genotype and the T allele of the CD14 gene were significantly associated (OR [95% CI]) with FD (2.65 [1.42-4.94] and 1.67 [1.23-2.26], respectively). The CT, TT genotypes, and T allele frequencies of GNB3 showed also significant association with FD (2.18 [1.35-3.54], 3.46 [1.30-9.23], and 2.18 [1.48-3.19]). While heterozygous GC MIF genotype was more common in dyspeptics (1.67 [1.07-2.60]), homozygous CC genotype and the C allele of TRPV1 gene were more prevalent in controls (0.47 [0.25-0.87] and 0.69 [0.51-0.92], respectively). None of the gene polymorphism was related either to dyspepsia clinical syndrome type or to the H. pylori infection. Among dyspeptics, CD14 TT genotype was related to lower epigastric pain burden score (p<.011); CD14 CT genotype was related to higher epigastric burning and nausea burden scores (p<.04) while belching score was lower (p=.027) in MIF CG dyspeptics. Functional dyspepsia susceptibility is related to CD14, GNB3, MIF, and TRPV1 gene polymorphisms, while CD14 and MIF gene variants are also associated with dyspepsia symptoms burden.

Gender Differences in the Alteration of Obesogenic Environments in Korean Children According to GNB3 Polymorphism

Background: A single-nucleotide polymorphism, C825T in the G protein β3 subunit (GNB3) gene, is associated with essential hypertension and obesity. However, the potential interaction of the GNB3C825T polymorphism with obesogenic environmentsin obesity of Korean children has not been closely evaluated yet. Methods: We analyzed data collected from 635 boys and 627 girls aged 8-9 yearsrecruited from seven elementary schools in Seoul, South Korea. Measures of anthropometry and blood pressure (BP) as well as fasting blood samples were used in the analysis. Three-day food records were collected. Results: Obese children had higher BP, lipid profiles and insulinresistance-related factors than did lean children. Higher body mass index (BMI), waist circumference (WC)and BP and lowerplasma lipid profiles were observed in boys than in girls. The genotype frequencies of the GNB3 polymorphism were CC=23.7%, CT=52.1%, and TT=24.2%, and the allele frequencies were C allele=49.7% and T allele=50.3 in the subjects. There was no significant difference according to gender and obesity with allelic frequencies. Boys with the T allele were more obese thanthose with the C allele, but the C and T alleles, according to anthropometrics and plasma variables, did not differ between the obesity and lean groups. In contrast to boys, obese girls with the T allele had lower BMI and WC than those with the C allele, although they had higher plasma cholesteroland energy intakes compared to those with the C allele. We found that the HDL3c subtype, fasting insulin and homeostasis model assessment of insulin resistance decreased with increasing HDL peak amount, which was positively correlated with total HDLcholesterol. However, the HDL subtypes were not changed by the GNB3 C825T polymorphism. Conclusion: The GNB3 C825T polymorphism influences the childhood obesity rate and energy intakesdifferentially by gender in Korean children.

Synergistic Effects of ACE Insertion/Deletion and GNB3 C825T Polymorphisms on the Efficacy of PDE-5 Inhibitor in Patients with Pulmonary Hypertension

Background: The insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) and the C825T polymorphism in the G-protein β3 subunit gene (GNB3) are associated with the efficacy of phosphodiesterase-5 inhibitor (PDE-5I) in erectile dysfunction. In addition, GNB3 genotypes could be associated with clinical worsening in pulmonary hypertension (PH) treated with PDE-5I. However, no studies have described the synergistic effects of gene polymorphisms on drug efficacy in patients with PH. Objectives: We aimed to examine the effects of combined ACE/GNB3 polymorphisms on the efficacy of PDE-5I in patients with PH. Methods: This was a retrospective uncontrolled study. Ninety patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic PH (CTEPH) were treated with PDE-5I. Freedom from clinical worsening and pre- and post-treatment parameters, including the 6-min walk distance (6MWD) and serum brain natriuretic peptide (BNP) levels, were compared between patients with ACE/GNB3 II/TT and non-II/TT genotypes. Results: Time to clinical worsening was significantly longer in patients with the II/TT genotype than in those with the non-II/TT genotype (5-year freedom from clinical worsening: 100 vs. 48.8%, respectively; p = 0.018), even in patients with CTEPH alone. Post-treatment 6MWD and BNP levels in patients with the II/TT genotype tended to be better than those in patients with the non-II/TT genotype. The ACE/GNB3 genotype was a significant predictor of clinical worsening, even after adjusting for pulmonary vascular resistance and 6MWD. Conclusions:ACE and GNB3 polymorphisms may synergistically influence the efficacy of PDE-5I in patients with PH.

Validation of G-protein beta-3 subunit gene C825T polymorphism as predictor of obesogenic epidemics in overweight/obese Korean children

Purpose: We investigated the potential interaction between the G-protein beta-3 subunit gene (GNB3) C825T polymorphism, a risk factor for chronic disease in various ethnicities, and obesogenic environments in overweight/obese Korean children. Methods: The present study was conducted as a cross-sectional study using measures of anthropometry, blood pressure (BP), and fasting blood samples as well as 3-day food records. Subjects were recruited from seven elementary schools in an urban district in Seoul, South Korea, between 2007 and 2008. A total of 1,260 children aged 8-9 years were recruited in the study, including 633 boys (50.3%) and 627 girls (49.7%). Results: The allele frequencies of the GNB3 polymorphism were C allele = 49.7% and T allele = 50.3% in subjects. In general, boys with T allele had higher BMI, systolic BP (SBP), and triglycerides, although their energy intake was not significantly different from boys with C allele. In contrast to boys, girls with T allele had lower BMI but higher SBP and energy intake than those with C allele. The girls with T allele had a significantly lower BMI and waist circumference in both the normal weight group and obese group (OB). T allele carriers in both genders had significantly higher TC than C allele carriers in the OB group. At last, girls with T allele in OB appeared to have significantly lower HOMA-IR than those with C allele. Conclusion: Unlike higher risk for negative health outcomes by the GNB3 polymorphism in various ethnicities, GNB3 polymorphism did not influence obesogenic environments in overweight/obese Korean children.