AIM To investigate whether GNB3 C825 T single nucleotide polymorphism(SNP) contributes to systolic blood pressure(SBP) ≥ 130 mmH g in a large-scale cross-sectional study among the Japanese population with diastolic b...AIM To investigate whether GNB3 C825 T single nucleotide polymorphism(SNP) contributes to systolic blood pressure(SBP) ≥ 130 mmH g in a large-scale cross-sectional study among the Japanese population with diastolic blood pressure(DBP) < 85 mmH g. METHODS We analyzed 11008 Japanese subjects, including 2797 cases(SBP ≥ 130 and DBP < 85 mmH g) who were not taking anti-hypertensive medication and 8211 controls(SBP < 130 and DBP < 85 mmH g), all of whom enrolled in the genome banking project of the 21 st Century COE(Center of Excellence) Program at Jichi Medical University. Subjects were divided into four groups according to gender(male and female) and age(≤ 49 years and ≥ 50 years). GNB3 gene polymorphism was determined using the TaqM an probe method. We compared the frequencies of alleles and genotypes between cases and controls by chi-squared test. The strength of the associations was estimated by odds ratios(ORs) and 95%CI by using logistic regression analysis. The ORs were adjusted for age and body mass index. RESULTS Allele and genotype distributions significantly differed between cases and controls only in males aged ≤ 49 years. Compared to the CC genotype, a significant OR was obtained in the TT genotype among males aged ≤ 49 years.CONCLUSION This study indicates that the TT genotype of the GNB3 C825 T SNP may contribute to SBP elevation of greater than 130 mmH g compared to the CC genotype in Japanese males aged ≤ 49 years.展开更多
Objective To explore the association between the three polymorphisms [ C825T, C1429T and G（-350）A] of the gene encoding the G protein beta 3 subunit （GNB3） and hypertension by performing a case-control study in th...Objective To explore the association between the three polymorphisms [ C825T, C1429T and G（-350）A] of the gene encoding the G protein beta 3 subunit （GNB3） and hypertension by performing a case-control study in the northern Han Chinese population. Methods We recnaited 731 hypertensive patients and 673 control subjects （the calculated power value was 〉 0.8）. Genotyping was performed to identify C825T, C1429T and G（-350）A polymorphisms using the TaqMan assay. Comparisons of allelic and genotypic frequencies between cases and controls were made by using the chi-square test. Logistic regression analyses were performed to investigate the relationships between the three polymorphisms of GNB3 gene under different genetic models （additive, dominant and recessive models）. Results The genotype dis- tribution and allele frequencies of C825T, C1429T and G（-350）A polymorphisms did not differ significantly between hypertensive patients and control subjects, either when the full sample was assessed, or when the sample was stratified by gender. No significant association was observed between C825T, C 1429T and G（-350）A polymorphisms and the risk of essential hypertension in any genetic model. Linkage dis- equilibrium was only detected between C825T and C 1429T polymorphisms. Haplotype analyses observed that none of the three estimated haplotypes significantly increased the risk of hypertension. Conclusions Our study suggested that the GNB3 gene polymorphisms [C825T, C 1429T and G（-350）A] were not significantly associated with essential hypertension in northern Han Chinese population.展开更多
BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bo...BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bowel syndrome(IBS).AIM To assess the association of HTR3 polymorphisms with depressive,anxiety,and somatization symptoms in individuals with IBS.METHODS In this retrospective study,623 participants with IBS were recruited from five specialty centers in Germany,Sweden,the United States,the United Kingdom,and Ireland.Depressive,anxiety,and somatization symptoms and sociodemographic characteristics were collected.Four functional SNPs—HTR3A c.-42C>T,HTR3B c.386A>C,HTR3C c.489C>A,and HTR3E c.*76G>A—were genotyped and analyzed using the dominant and recessive models.We also performed separate analyses for sex and IBS subtypes.SNP scores were calculated as the number of minor alleles of the SNPs above.The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays.RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model(F_(depressive)=7.475,P_(depressive)=0.006;F_(anxiety)=6.535,P_(anxiety)=0.011).A higher SNP score(range 0-6)was linked to a worsened depressive symptoms score(F=7.710,P-linear trend=0.006)in IBS.The potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant receptors.CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS.The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.展开更多
Zika virus(ZIKV),a positive-sense single-stranded RNA virus,causes congenital ZIKV syndrome in children and Guillain-Barre Syndrome(GBS)in adults.ZIKV expresses nonstructural protein 5(NS5),a large protein that is ess...Zika virus(ZIKV),a positive-sense single-stranded RNA virus,causes congenital ZIKV syndrome in children and Guillain-Barre Syndrome(GBS)in adults.ZIKV expresses nonstructural protein 5(NS5),a large protein that is essential for viral replication.ZIKV NS5 confers the ability to evade interferon(IFN)signalling;however,the exact mechanism remains unclear.In this study,we employed affinity pull-down and liquid chromatography-tandem mass spectrometry(LC-MS/MS)analyses and found that splicing factor 3b subunit 3(SF3B3)is associated with the NS5-Flag pull-down complex through interaction with NS5.Functional assays showed that SF3B3 overexpression inhibited ZIKV replication by promoting IFN-stimulated gene(ISG)expression whereas silencing of SF3B3 inhibited expression of ISGs to promote ZIKV replication.GTP cyclohydrolase I(GCH1)is the first and ratelimiting enzyme in tetrahydrobiopterin(BH4)biosynthesis.NS5 upregulates the expression of GCH1 during ZIKV infection.And GCH1 marginally promoted ZIKV replication via the IFN pathway.Additionally,GCH1 expression is related to the regulation of SF3B3.Overexpression of the SF3B3 protein effectively reduced GCH1 protein levels,whereas SF3B3 knockdown increased its levels.These findings indicated that ZIKV NS5 binding protein SF3B3 contributed to the host immune response against ZIKV replication by modulating the expression of GCH1.展开更多
基金Supported by The Jichi Medical University 21st Century Center of Excellence Program from Minister Education,Culture,Sports,Science and Technology in Japan
文摘AIM To investigate whether GNB3 C825 T single nucleotide polymorphism(SNP) contributes to systolic blood pressure(SBP) ≥ 130 mmH g in a large-scale cross-sectional study among the Japanese population with diastolic blood pressure(DBP) < 85 mmH g. METHODS We analyzed 11008 Japanese subjects, including 2797 cases(SBP ≥ 130 and DBP < 85 mmH g) who were not taking anti-hypertensive medication and 8211 controls(SBP < 130 and DBP < 85 mmH g), all of whom enrolled in the genome banking project of the 21 st Century COE(Center of Excellence) Program at Jichi Medical University. Subjects were divided into four groups according to gender(male and female) and age(≤ 49 years and ≥ 50 years). GNB3 gene polymorphism was determined using the TaqM an probe method. We compared the frequencies of alleles and genotypes between cases and controls by chi-squared test. The strength of the associations was estimated by odds ratios(ORs) and 95%CI by using logistic regression analysis. The ORs were adjusted for age and body mass index. RESULTS Allele and genotype distributions significantly differed between cases and controls only in males aged ≤ 49 years. Compared to the CC genotype, a significant OR was obtained in the TT genotype among males aged ≤ 49 years.CONCLUSION This study indicates that the TT genotype of the GNB3 C825 T SNP may contribute to SBP elevation of greater than 130 mmH g compared to the CC genotype in Japanese males aged ≤ 49 years.
基金grants of the National High Technology Research and Development Program，grants of the National Eleventh Five-year Plan Program from the Ministry of Science and Technology of China，Beijing Natural Science Foundation
文摘Objective To explore the association between the three polymorphisms [ C825T, C1429T and G（-350）A] of the gene encoding the G protein beta 3 subunit （GNB3） and hypertension by performing a case-control study in the northern Han Chinese population. Methods We recnaited 731 hypertensive patients and 673 control subjects （the calculated power value was 〉 0.8）. Genotyping was performed to identify C825T, C1429T and G（-350）A polymorphisms using the TaqMan assay. Comparisons of allelic and genotypic frequencies between cases and controls were made by using the chi-square test. Logistic regression analyses were performed to investigate the relationships between the three polymorphisms of GNB3 gene under different genetic models （additive, dominant and recessive models）. Results The genotype dis- tribution and allele frequencies of C825T, C1429T and G（-350）A polymorphisms did not differ significantly between hypertensive patients and control subjects, either when the full sample was assessed, or when the sample was stratified by gender. No significant association was observed between C825T, C 1429T and G（-350）A polymorphisms and the risk of essential hypertension in any genetic model. Linkage dis- equilibrium was only detected between C825T and C 1429T polymorphisms. Haplotype analyses observed that none of the three estimated haplotypes significantly increased the risk of hypertension. Conclusions Our study suggested that the GNB3 gene polymorphisms [C825T, C 1429T and G（-350）A] were not significantly associated with essential hypertension in northern Han Chinese population.
基金results in part from collaboration and network activities promoted under the frame of the international network GENIEUR (Genes in Irritable Bowel Syndrome Research Network Europe),which has been funded by the COST program (BM1106, www.GENIEUR.eu)currently supported by the European Society of Neurogastroenterology and Motility (ESNM, www.ESNM.eu)
文摘BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bowel syndrome(IBS).AIM To assess the association of HTR3 polymorphisms with depressive,anxiety,and somatization symptoms in individuals with IBS.METHODS In this retrospective study,623 participants with IBS were recruited from five specialty centers in Germany,Sweden,the United States,the United Kingdom,and Ireland.Depressive,anxiety,and somatization symptoms and sociodemographic characteristics were collected.Four functional SNPs—HTR3A c.-42C>T,HTR3B c.386A>C,HTR3C c.489C>A,and HTR3E c.*76G>A—were genotyped and analyzed using the dominant and recessive models.We also performed separate analyses for sex and IBS subtypes.SNP scores were calculated as the number of minor alleles of the SNPs above.The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays.RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model(F_(depressive)=7.475,P_(depressive)=0.006;F_(anxiety)=6.535,P_(anxiety)=0.011).A higher SNP score(range 0-6)was linked to a worsened depressive symptoms score(F=7.710,P-linear trend=0.006)in IBS.The potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant receptors.CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS.The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.
基金supported by the National Key R&D Project of China(2021YFC230170402)CAMS Innovation Fund for Medical Sciences(2021-1-I2M-038).
文摘Zika virus(ZIKV),a positive-sense single-stranded RNA virus,causes congenital ZIKV syndrome in children and Guillain-Barre Syndrome(GBS)in adults.ZIKV expresses nonstructural protein 5(NS5),a large protein that is essential for viral replication.ZIKV NS5 confers the ability to evade interferon(IFN)signalling;however,the exact mechanism remains unclear.In this study,we employed affinity pull-down and liquid chromatography-tandem mass spectrometry(LC-MS/MS)analyses and found that splicing factor 3b subunit 3(SF3B3)is associated with the NS5-Flag pull-down complex through interaction with NS5.Functional assays showed that SF3B3 overexpression inhibited ZIKV replication by promoting IFN-stimulated gene(ISG)expression whereas silencing of SF3B3 inhibited expression of ISGs to promote ZIKV replication.GTP cyclohydrolase I(GCH1)is the first and ratelimiting enzyme in tetrahydrobiopterin(BH4)biosynthesis.NS5 upregulates the expression of GCH1 during ZIKV infection.And GCH1 marginally promoted ZIKV replication via the IFN pathway.Additionally,GCH1 expression is related to the regulation of SF3B3.Overexpression of the SF3B3 protein effectively reduced GCH1 protein levels,whereas SF3B3 knockdown increased its levels.These findings indicated that ZIKV NS5 binding protein SF3B3 contributed to the host immune response against ZIKV replication by modulating the expression of GCH1.
