Objective:?Although several NPHS2 gene mutations and polymorphisms were described and?associated with clinical manifestation of steroid-resistant nephrotic syndrome (SRNS),?the?occurrence of these genetic abnormalitie...Objective:?Although several NPHS2 gene mutations and polymorphisms were described and?associated with clinical manifestation of steroid-resistant nephrotic syndrome (SRNS),?the?occurrence of these genetic abnormalities or variants appeared?to be influenced by race and ethnic group. We have investigated?probable mutations and variants in NPHS2 gene involved in SRNS and their association with clinical manifestations. Methods: We examined 28 children?with primary SRNS?whovisited?the pediatric nephrology division of 10 teaching hospitals in Indonesia. Molecular genetic studies of the NPHS2 gene were?conducted through screenings?for the exon 1, exon 2, and exon 8. The mutational analysis of NPHS2 was performed by DNA sequencing.?Fisher’s Exact Test was used to determine?the?correlation?between?NPHS2 polymorphisms and clinical manifestations.Results:?Seven?females (25%) and 21 males (75%)?participated in the study.?The mean age of the subjects with 95% CI is: 7.6 (6.1 - 9.0) years while the mean age at onset of disease with 95% CI is: 5.4 (3.9 - 7.0) years. Sixteen patients (57.14%) were younger than 6 years at the onset of disease. Seventeen (60.7%) subjects had normal eGFR, while 11 (39.3%) had chronic renal insufficiency. The mean eGFR of the subjects with 95% CI is: 111.4 (87.7 - 135.1) ml/min/1.73 m2. The mean systolic blood pressure with 95% CI is: 117.0 (108.9 - 125.1) mmHg and the mean diastolic blood pressure with 95% CI is: 77.0 (70.3 - 83.7) mmHg.?We identified 6 NPHS2polymorphisms,?i.e.?g.-52G>T, c.101A>G, g.-117C>T, c.288C>T, c.954C>T, and c.1038A>G and no mutation?was found. There was?no correlation?between?NPHS2 polymorphisms and clinical manifestations (p > 0.05). Conclusion: The?results demonstrate no mutation of NPHS2 gene, and the 6 NPHS2 gene polymorphisms that were identified have no correlation with the clinical manifestation in Indonesian children with SRNS.展开更多
Objective Idiopathic nephrotic syndrome(INS)is the most common glomerular disease in children.Toll-like receptors(TLRs)have been reported to be associated with response to steroid treatment in children with INS.Nevert...Objective Idiopathic nephrotic syndrome(INS)is the most common glomerular disease in children.Toll-like receptors(TLRs)have been reported to be associated with response to steroid treatment in children with INS.Nevertheless,the correlation between TLR genes and the progression of INS has not yet been clarified.The present study aimed to investigate the association of single-nucleotide polymorphisms(SNPs)in TLR2,TLR4,and TLR9 with susceptibility to INS as well as the clinical phenotyping of steroid responsiveness in Chinese children with INS.Methods A total of 183 pediatric inpatients with INS were included and given standard steroid therapy.Based on their clinical response to steroids,the patients were classified into three groups:steroid-sensitive nephrotic syndrome(SSNS),steroid-dependent nephrotic syndrome(SDNS),and steroid-resistant nephrotic syndrome(SRNS).A total of 100 healthy children were employed as controls.The blood genome DNA was extracted from each participant.Six SNPs(rs11536889,rs1927914,rs7869402,rs11536891,rs352140,and rs3804099)in TLR2,TLR4,and TLR9 were selected and detected by multiplex polymerase chain reaction with next-generation sequencing to assess TLR gene polymorphisms.Results Among the 183 patients with INS,89(48.6%)had SSNS,73(39.9%)had SDNS,and 21(11.5%)had SRNS.No significant difference was found in the genotype distribution between healthy children and patients with INS.However,the genotype and allele frequencies of TLR4 rs7869402 were significantly different between SRNS and SSNS.Compared with patients with the C allele and CC genotype,patients with the T allele and CT genotype had an increased risk of SRNS.Conclusion TLR4 rs7869402 affected the steroid response in Chinese children with INS.It might be a predictor for the early detection of SRNS in this population.展开更多
Summary: To determine the (tttta) n repeat polymorphisms at the promoter region of CYP11α gene, and study its linkage to hyperandrogenism of polycystic ovary syndrome (PCOS) in Chinese women, a case-control study w...Summary: To determine the (tttta) n repeat polymorphisms at the promoter region of CYP11α gene, and study its linkage to hyperandrogenism of polycystic ovary syndrome (PCOS) in Chinese women, a case-control study was conducted in the Reproductive Medical Center of the Second Affiliated Hospital of Zhengzhou University (Zhengzhou, China). 96 PCOS patients and 78 healthy control women were included. CYP11α (tttta) n repeat-polymorphism genotyping analysis was performed by using polymerase chain reaction (PCR). Serum pituitary hormone and total testosterone levels were measured by ELISA. 4 different CYP11α (tttta) n allelles were identified, corresponding to 4-, 6-, 8-, and 9-repeat-unit alleles. The frequency and distribution of these alleles are 0.16, 0.33, 0.38, and 0.13 respectively in PCOS patients, as compared with 0.20, 0.34, 0.35, and 0.11 respectively in healthy controls. There were no significant differences between these two groups. Moreover, no correlation between the polymorphism of CYP11α gene and serum testosterone level of patients with PCOS and controls was observed. It is concluded that microsatellite polymorphism (tttta) n of gene CYP11α exists in Chinese women and the polymorphism of CYP11α gene does not play an important role in the pathogenesis of Chinese patients with PCOS, especially in patients with hyperandrogenism.展开更多
Irritable bowel syndrome （IBS） is a common functional gastrointestinal disorder. According to the Rome m criteria, IBS is defined as recurrent abdominal pain or discomfort for at least 3 d per month during the previ...Irritable bowel syndrome （IBS） is a common functional gastrointestinal disorder. According to the Rome m criteria, IBS is defined as recurrent abdominal pain or discomfort for at least 3 d per month during the previous 3 mo associated with two or more of the following symptoms： improvement with defecation, onset associated with a change in the frequency of stool and/or onset associated with a change in form or appearance of stool. There is growing evidence regarding the genetic contribution in IBS, however the precise etiology of IBS is still unknown. The evaluation of the genetic influence is based on twin studies, familial aggregation and genetic epidemiological investigations. Most studies showed a concordance for IBS significantly greater in monozygotic than in dizygotic twins. The majority of the studies have shown that familial aggregation may represent exposures to a similar environment, as well as the influence of genetic factors. Whereas no specific gene has been identified in association with IBS, recent studies have noticed the importance of polymorphisms in the promoter region of the serotonin reuptake transporter gene, G-protein beta 3 subunit gene （C825T）, cholecystokinin receptor （CCKAR gene 779T〉C）, and high-producer tumor necrosis factor genotype. Further studies are necessary to determine how genetic factors influence the clinical manifestations and therapeutical response in IBS patients.展开更多
Nephrotic syndrome(NS)is relatively common in children,with most of its histological types being minimal changed disease.Its etiology has long been attributed to lymphocyte(especially T-cell)dysfunction,while T-cell-m...Nephrotic syndrome(NS)is relatively common in children,with most of its histological types being minimal changed disease.Its etiology has long been attributed to lymphocyte(especially T-cell)dysfunction,while T-cell-mediated vascular hyperpermeability increases protein permeability in glomerular capillaries,leading to proteinuria and hypoproteinemia.Based on this etiology,steroids and immunosuppressive drugs that are effective against this disease have also been considered to correct T-cell dysfunction.However,in recent years,this has been questioned.The primary cause of NS has been considered damage to glomerular epithelial cells and podocyte-related proteins.Therefore,we first describe the changes in expression of molecules involved in NS etiology,and then describe the mechanism by which abnormal expression of these molecules induces proteinuria.Finally,we consider the mechanism by which infection causes the recurrence of NS.展开更多
AIM To evaluate the most common studied genetic polymorphisms that may have an etiological role in irritable bowel syndrome (IBS).METHODS The data base Pub Med was searched for studies analyzing the association betwee...AIM To evaluate the most common studied genetic polymorphisms that may have an etiological role in irritable bowel syndrome (IBS).METHODS The data base Pub Med was searched for studies analyzing the association between gene polymorphisms and IBS. All original full papers, written in English, were retained for further analysis. The retrieved papers were further systematized according to those polymorphisms that have been detected in IBS.RESULTS Considering these criteria, our literature search found 12 polymorphisms, residing in 10 genes, which were reported to be consistently associated with IBS. The initial search identified 189 articles, out of which 48 potentially appropriate articles were reviewed. Of these 48 articles, 41 articles were included in the review. These articles were published between 2002 and 2016. Out of these 41 studies, 17 reported analysis of the serotonin transporter (SERT) gene (SLC6A4), eight on guanine nucleotide-binding protein subunit beta-3 (GNbeta3), six on the serotonin type 3 receptor genes (HTR3A), four on (HTR3E), three on (HTR2A), three the tumor necrosis factor superfamily member TL1A gene (TNFSF15), and ten on genetic polymorphisms with limited evidence.CONCLUSION Current evidence for the relation between genetic polymorphisms and IBS is limited owing to the fact that high-quality prospective studies and detailed phenotyping of patients suffering from IBS and matched controls were lacking in the past.展开更多
Background Mutations in the cardiac sodium channel gene (SCN5A) may lead to a broad spectrum of familial arrhythmias, including long QT syndrome (LQTS), idiopathic ventricular fibrillation (IVF), and isolated cardiac...Background Mutations in the cardiac sodium channel gene (SCN5A) may lead to a broad spectrum of familial arrhythmias, including long QT syndrome (LQTS), idiopathic ventricular fibrillation (IVF), and isolated cardiac conduction diseases Recent studies have shown that polymorphisms in the SCN5A gene also play an important role in the manifestation of disorders involving cardiac excitability In this study, we investigated the polymorphisms of the SCN5A gene in Han Chinese and its relation to Brugada syndrome (BS) Methods Genomic DNA was isolated from 120 unrelated healthy volunteers and 48 unrelated Brugada syndrome patients by means of standard procedures All exons including the putative splicing sites of the SCN5A gene were amplified by PCR and sequenced directly or after subcloning using an ABI Prism 377 DNA sequencer Results A total of 5 single nucleotide polymorphisms (SNPs) were identified in the Han Chinese population, including 3 novel ones: G87A(A29A), 4245+82A>G, and G6174A The allele frequencies of each SNP in the Han Chinese population were as follows: G87A (A29A) 27 5%, A1673G (H558R) 10 4%, 4245+82A>G 32 8%, C5457T (D1819D) 41 3%, and G6174A 44 9% S1102Y and 10 other SNPs identified in other ethnic populations were not detected in this study There was no significant difference in the allele frequency of A1673G (H558R) between different ethnic populations (all P >0 5) On the other hand, the allele frequency of C5457T (D1819D) among Han Chinese was similar to its frequency among Japanese ( P >0 5), but higher than that among Americans ( P <0 005) The allele G1673 (R558) was over-represented in BS patients compared to controls ( P <0 005), but there was no significant difference in genotype frequencies at this locus There were also no differences in either the allele or genotype frequencies of the 4 other identified SNPs when comparing BS patients with healthy controls Conclusions The distribution of SCN5A SNPs may vary between different ethnicities The polymorphism of A1673G might be associated with BS and may contribute to a susceptibility to BS in Han Chinese展开更多
多囊卵巢综合征(PCOS)是一种复杂的生殖内分泌疾病,主要特征是月经稀发或闭经、高雄激素血症以及卵巢多囊样改变。遗传因素在PCOS发病中的重要作用已经得到证实,许多候选基因也被识别。目前发现的易感基因主要包括参与甾体激素生物合成...多囊卵巢综合征(PCOS)是一种复杂的生殖内分泌疾病,主要特征是月经稀发或闭经、高雄激素血症以及卵巢多囊样改变。遗传因素在PCOS发病中的重要作用已经得到证实,许多候选基因也被识别。目前发现的易感基因主要包括参与甾体激素生物合成、转运、作用和调节的相关基因,慢性炎症相关基因,胰岛素抵抗和转化生长因子β(TGF-β)通路相关基因等。全基因组关联研究(genome-wide association study,GWAS)为了解PCOS的发病机制提供了新方向。然而,由于PCOS患者基因和表型复杂,目前遗传学研究仍未得出明确结论。现对PCOS遗传学研究最新进展进行综述。展开更多
文摘Objective:?Although several NPHS2 gene mutations and polymorphisms were described and?associated with clinical manifestation of steroid-resistant nephrotic syndrome (SRNS),?the?occurrence of these genetic abnormalities or variants appeared?to be influenced by race and ethnic group. We have investigated?probable mutations and variants in NPHS2 gene involved in SRNS and their association with clinical manifestations. Methods: We examined 28 children?with primary SRNS?whovisited?the pediatric nephrology division of 10 teaching hospitals in Indonesia. Molecular genetic studies of the NPHS2 gene were?conducted through screenings?for the exon 1, exon 2, and exon 8. The mutational analysis of NPHS2 was performed by DNA sequencing.?Fisher’s Exact Test was used to determine?the?correlation?between?NPHS2 polymorphisms and clinical manifestations.Results:?Seven?females (25%) and 21 males (75%)?participated in the study.?The mean age of the subjects with 95% CI is: 7.6 (6.1 - 9.0) years while the mean age at onset of disease with 95% CI is: 5.4 (3.9 - 7.0) years. Sixteen patients (57.14%) were younger than 6 years at the onset of disease. Seventeen (60.7%) subjects had normal eGFR, while 11 (39.3%) had chronic renal insufficiency. The mean eGFR of the subjects with 95% CI is: 111.4 (87.7 - 135.1) ml/min/1.73 m2. The mean systolic blood pressure with 95% CI is: 117.0 (108.9 - 125.1) mmHg and the mean diastolic blood pressure with 95% CI is: 77.0 (70.3 - 83.7) mmHg.?We identified 6 NPHS2polymorphisms,?i.e.?g.-52G>T, c.101A>G, g.-117C>T, c.288C>T, c.954C>T, and c.1038A>G and no mutation?was found. There was?no correlation?between?NPHS2 polymorphisms and clinical manifestations (p > 0.05). Conclusion: The?results demonstrate no mutation of NPHS2 gene, and the 6 NPHS2 gene polymorphisms that were identified have no correlation with the clinical manifestation in Indonesian children with SRNS.
基金This study was funded by the Science and Technology Projects of Zhejiang Province(No.LGC21H200004)the Key Research and Development Plan of Zhejiang Province(No.2019C03028)the Medical Scientific Projects from Health Department of Zhejiang Province(No.2018KY455)。
文摘Objective Idiopathic nephrotic syndrome(INS)is the most common glomerular disease in children.Toll-like receptors(TLRs)have been reported to be associated with response to steroid treatment in children with INS.Nevertheless,the correlation between TLR genes and the progression of INS has not yet been clarified.The present study aimed to investigate the association of single-nucleotide polymorphisms(SNPs)in TLR2,TLR4,and TLR9 with susceptibility to INS as well as the clinical phenotyping of steroid responsiveness in Chinese children with INS.Methods A total of 183 pediatric inpatients with INS were included and given standard steroid therapy.Based on their clinical response to steroids,the patients were classified into three groups:steroid-sensitive nephrotic syndrome(SSNS),steroid-dependent nephrotic syndrome(SDNS),and steroid-resistant nephrotic syndrome(SRNS).A total of 100 healthy children were employed as controls.The blood genome DNA was extracted from each participant.Six SNPs(rs11536889,rs1927914,rs7869402,rs11536891,rs352140,and rs3804099)in TLR2,TLR4,and TLR9 were selected and detected by multiplex polymerase chain reaction with next-generation sequencing to assess TLR gene polymorphisms.Results Among the 183 patients with INS,89(48.6%)had SSNS,73(39.9%)had SDNS,and 21(11.5%)had SRNS.No significant difference was found in the genotype distribution between healthy children and patients with INS.However,the genotype and allele frequencies of TLR4 rs7869402 were significantly different between SRNS and SSNS.Compared with patients with the C allele and CC genotype,patients with the T allele and CT genotype had an increased risk of SRNS.Conclusion TLR4 rs7869402 affected the steroid response in Chinese children with INS.It might be a predictor for the early detection of SRNS in this population.
基金This project was supported by a grant of Henan Provincial Bureau of Science and Technology (No. 0424410097).
文摘Summary: To determine the (tttta) n repeat polymorphisms at the promoter region of CYP11α gene, and study its linkage to hyperandrogenism of polycystic ovary syndrome (PCOS) in Chinese women, a case-control study was conducted in the Reproductive Medical Center of the Second Affiliated Hospital of Zhengzhou University (Zhengzhou, China). 96 PCOS patients and 78 healthy control women were included. CYP11α (tttta) n repeat-polymorphism genotyping analysis was performed by using polymerase chain reaction (PCR). Serum pituitary hormone and total testosterone levels were measured by ELISA. 4 different CYP11α (tttta) n allelles were identified, corresponding to 4-, 6-, 8-, and 9-repeat-unit alleles. The frequency and distribution of these alleles are 0.16, 0.33, 0.38, and 0.13 respectively in PCOS patients, as compared with 0.20, 0.34, 0.35, and 0.11 respectively in healthy controls. There were no significant differences between these two groups. Moreover, no correlation between the polymorphism of CYP11α gene and serum testosterone level of patients with PCOS and controls was observed. It is concluded that microsatellite polymorphism (tttta) n of gene CYP11α exists in Chinese women and the polymorphism of CYP11α gene does not play an important role in the pathogenesis of Chinese patients with PCOS, especially in patients with hyperandrogenism.
文摘Irritable bowel syndrome （IBS） is a common functional gastrointestinal disorder. According to the Rome m criteria, IBS is defined as recurrent abdominal pain or discomfort for at least 3 d per month during the previous 3 mo associated with two or more of the following symptoms： improvement with defecation, onset associated with a change in the frequency of stool and/or onset associated with a change in form or appearance of stool. There is growing evidence regarding the genetic contribution in IBS, however the precise etiology of IBS is still unknown. The evaluation of the genetic influence is based on twin studies, familial aggregation and genetic epidemiological investigations. Most studies showed a concordance for IBS significantly greater in monozygotic than in dizygotic twins. The majority of the studies have shown that familial aggregation may represent exposures to a similar environment, as well as the influence of genetic factors. Whereas no specific gene has been identified in association with IBS, recent studies have noticed the importance of polymorphisms in the promoter region of the serotonin reuptake transporter gene, G-protein beta 3 subunit gene （C825T）, cholecystokinin receptor （CCKAR gene 779T〉C）, and high-producer tumor necrosis factor genotype. Further studies are necessary to determine how genetic factors influence the clinical manifestations and therapeutical response in IBS patients.
文摘Nephrotic syndrome(NS)is relatively common in children,with most of its histological types being minimal changed disease.Its etiology has long been attributed to lymphocyte(especially T-cell)dysfunction,while T-cell-mediated vascular hyperpermeability increases protein permeability in glomerular capillaries,leading to proteinuria and hypoproteinemia.Based on this etiology,steroids and immunosuppressive drugs that are effective against this disease have also been considered to correct T-cell dysfunction.However,in recent years,this has been questioned.The primary cause of NS has been considered damage to glomerular epithelial cells and podocyte-related proteins.Therefore,we first describe the changes in expression of molecules involved in NS etiology,and then describe the mechanism by which abnormal expression of these molecules induces proteinuria.Finally,we consider the mechanism by which infection causes the recurrence of NS.
基金funded by the COST program[BM1106,(www.GENIEUR.eu)]supported by the European Society of Neurogastroenterology and Motility(ESNM,www.ESNM.eu)
文摘AIM To evaluate the most common studied genetic polymorphisms that may have an etiological role in irritable bowel syndrome (IBS).METHODS The data base Pub Med was searched for studies analyzing the association between gene polymorphisms and IBS. All original full papers, written in English, were retained for further analysis. The retrieved papers were further systematized according to those polymorphisms that have been detected in IBS.RESULTS Considering these criteria, our literature search found 12 polymorphisms, residing in 10 genes, which were reported to be consistently associated with IBS. The initial search identified 189 articles, out of which 48 potentially appropriate articles were reviewed. Of these 48 articles, 41 articles were included in the review. These articles were published between 2002 and 2016. Out of these 41 studies, 17 reported analysis of the serotonin transporter (SERT) gene (SLC6A4), eight on guanine nucleotide-binding protein subunit beta-3 (GNbeta3), six on the serotonin type 3 receptor genes (HTR3A), four on (HTR3E), three on (HTR2A), three the tumor necrosis factor superfamily member TL1A gene (TNFSF15), and ten on genetic polymorphisms with limited evidence.CONCLUSION Current evidence for the relation between genetic polymorphisms and IBS is limited owing to the fact that high-quality prospective studies and detailed phenotyping of patients suffering from IBS and matched controls were lacking in the past.
文摘Background Mutations in the cardiac sodium channel gene (SCN5A) may lead to a broad spectrum of familial arrhythmias, including long QT syndrome (LQTS), idiopathic ventricular fibrillation (IVF), and isolated cardiac conduction diseases Recent studies have shown that polymorphisms in the SCN5A gene also play an important role in the manifestation of disorders involving cardiac excitability In this study, we investigated the polymorphisms of the SCN5A gene in Han Chinese and its relation to Brugada syndrome (BS) Methods Genomic DNA was isolated from 120 unrelated healthy volunteers and 48 unrelated Brugada syndrome patients by means of standard procedures All exons including the putative splicing sites of the SCN5A gene were amplified by PCR and sequenced directly or after subcloning using an ABI Prism 377 DNA sequencer Results A total of 5 single nucleotide polymorphisms (SNPs) were identified in the Han Chinese population, including 3 novel ones: G87A(A29A), 4245+82A>G, and G6174A The allele frequencies of each SNP in the Han Chinese population were as follows: G87A (A29A) 27 5%, A1673G (H558R) 10 4%, 4245+82A>G 32 8%, C5457T (D1819D) 41 3%, and G6174A 44 9% S1102Y and 10 other SNPs identified in other ethnic populations were not detected in this study There was no significant difference in the allele frequency of A1673G (H558R) between different ethnic populations (all P >0 5) On the other hand, the allele frequency of C5457T (D1819D) among Han Chinese was similar to its frequency among Japanese ( P >0 5), but higher than that among Americans ( P <0 005) The allele G1673 (R558) was over-represented in BS patients compared to controls ( P <0 005), but there was no significant difference in genotype frequencies at this locus There were also no differences in either the allele or genotype frequencies of the 4 other identified SNPs when comparing BS patients with healthy controls Conclusions The distribution of SCN5A SNPs may vary between different ethnicities The polymorphism of A1673G might be associated with BS and may contribute to a susceptibility to BS in Han Chinese
基金supported by Natural Science Foundation of Yunnan Science and Technology Committee(2007C223M2009CD)Natural Science Foundation of Yunnan Provincial Department of Education(07Z10336)
文摘多囊卵巢综合征(PCOS)是一种复杂的生殖内分泌疾病,主要特征是月经稀发或闭经、高雄激素血症以及卵巢多囊样改变。遗传因素在PCOS发病中的重要作用已经得到证实,许多候选基因也被识别。目前发现的易感基因主要包括参与甾体激素生物合成、转运、作用和调节的相关基因,慢性炎症相关基因,胰岛素抵抗和转化生长因子β(TGF-β)通路相关基因等。全基因组关联研究(genome-wide association study,GWAS)为了解PCOS的发病机制提供了新方向。然而,由于PCOS患者基因和表型复杂,目前遗传学研究仍未得出明确结论。现对PCOS遗传学研究最新进展进行综述。
