AIM:To investigate a possible genetic influence of claudin(CLDN)1,CLDN2 and CLDN4 in the etiology of inflammatory bowel disease.METHODS:Allelic association between genetic regions of CLDN1,CLDN2 or CLDN4 and patients ...AIM:To investigate a possible genetic influence of claudin(CLDN)1,CLDN2 and CLDN4 in the etiology of inflammatory bowel disease.METHODS:Allelic association between genetic regions of CLDN1,CLDN2 or CLDN4 and patients with inflammatory bowel disease,Crohn's disease(CD)or ulcerative colitis were investigated using both a casecontrol study approach(one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls)and a family-based study(463 non-Swedish European inflammatory bowel disease-families).A nonsynonymous coding single nucleotide polymorphism in MORC4,located on the same linkage block as CLDN2,was investigated for association,as were two novel CLDN2 single nucleotide polymorphism markers,identified by resequencing.RESULTS:A single nucleotide polymorphism marker(rs12014762)located in the genetic region of CLDN2 was significantly associated to CD(case-control allelic OR = 1.98,95%CI:1.17-3.35,P = 0.007).MORC4 was present on the same linkage block as this CD marker.Using the case-control approach,a significant association(case control allelic OR = 1.61,95%CI:1.08-2.41,P = 0.018)was found between CD and a nonsynonymous coding single nucleotide polymorphism(rs6622126)in MORC4.The association between the CLDN2 marker and CD was not replicated in the familybased study.Ulcerative colitis was not associated to any of the single nucleotide polymorphism markers.CONCLUSION:These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.展开更多
rs6311 and rs6313 are two Single Nucleotide Polymorphisms (SNPs) on the Serotonin Receptor 2A gene (5-HTR2A) in complete linkage disequilibrium. Numerous gene association studies have examined the relationships betwee...rs6311 and rs6313 are two Single Nucleotide Polymorphisms (SNPs) on the Serotonin Receptor 2A gene (5-HTR2A) in complete linkage disequilibrium. Numerous gene association studies have examined the relationships between one or both of these two polymorphisms and Major Depressive Disorder (MDD), with conflicting results. The present meta-analysis examined 19 case-control gene association studies, 9 of which included rs6311 (n = 3382), and 15 of which included rs6313 (n = 5590). The strength of relationship with MDD was assessed by pooled odds ratios and 95% confidence intervals for both SNPs according to four genetic models. Heterogeneity was measured by Q and I<sup>2</sup>. Subgrouping was performed by minor allele and by ethnicity. Results were nonsignificant for all models and subgroups, suggesting that genotype alone does not play a major role in genetic susceptibility to depression. The potential for epistatic, epigenetic, and regulatory RNA interactions with these SNPs is discussed, and future areas of research are recommended.展开更多
Gastric cancer is the most common malignancy of the gastrointestinal tract in East Asian populations and the second most frequent cause of cancer-related mortality in the world. While previous studies have investigate...Gastric cancer is the most common malignancy of the gastrointestinal tract in East Asian populations and the second most frequent cause of cancer-related mortality in the world. While previous studies have investigated the genetic factors involved in gastric carcinogenesis, there still exist relatively few studies that have investigated the genetic traits associated with the risk of gastric precancerous conditions. In this paper we will review the biology and genetic polymorphisms involved in the genesis of gastric precancerous conditions reported to date and discuss the future prospects of this field of study. The associations of gastric precancerous conditions with polymorphisms in the cytotoxin-associated gene A-related genes (e.g. PTPN11 G/A at intron 3, rs2301756), those in the genes involved in host immunity against Helico-bacter pylori (H. pylori) infection (e.g.TLR4 +3725G/C, rs11536889) or polymorphisms of the genes essential for the development/ differentiation of the gastric epithelial cells (e.g. RUNX3 T/A polymorphism at intron 3, rs760805) have been reported to date. Genetic epide-miological studies of the associations between H. pylori-induced gastric precancerous conditions and other gene polymorphisms in these pathways as well as polymor-phisms of the genes involved in other pathways like oxidative DNA damage repair pathways would provide useful evidence for the individualized prevention of these H. pylori-induced gastric precancerous conditions.展开更多
Colorectal cancer(CRC)is one of the most frequent neoplasms and an important cause of mortality in the developed world.This cancer is caused by both genetic and environmental factors although 35%of the variation in CR...Colorectal cancer(CRC)is one of the most frequent neoplasms and an important cause of mortality in the developed world.This cancer is caused by both genetic and environmental factors although 35%of the variation in CRC susceptibility involves inherited genetic differences.Mendelian syndromes account for about5%of the total burden of CRC,with Lynch syndrome and familial adenomatous polyposis the most common forms.Excluding hereditary forms,there is an important fraction of CRC cases that present familial aggregation for the disease with an unknown germline genetic cause.CRC can be also considered as a complex disease taking into account the common diseasecommom variant hypothesis with a polygenic model of inheritance where the genetic components of common complex diseases correspond mostly to variants of low/moderate effect.So far,30 common,low-penetrance susceptibility variants have been identified for CRC.Recently,new sequencing technologies including exomeand whole-genome sequencing have permitted to add a new approach to facilitate the identification of new genes responsible for human disease predisposition.By using whole-genome sequencing,germline mutations in the POLE and POLD1 genes have been found to be responsible for a new form of CRC genetic predisposition called polymerase proofreading-associated polyposis.展开更多
基金Supported by Grants from Futurum - the academy of healthcare,County council of Jnkpingthe Swedish Society of Medicinethe Research Council of South-East Sweden (FORSS) and the County Council of sterg tland (ALF-Grants)
文摘AIM:To investigate a possible genetic influence of claudin(CLDN)1,CLDN2 and CLDN4 in the etiology of inflammatory bowel disease.METHODS:Allelic association between genetic regions of CLDN1,CLDN2 or CLDN4 and patients with inflammatory bowel disease,Crohn's disease(CD)or ulcerative colitis were investigated using both a casecontrol study approach(one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls)and a family-based study(463 non-Swedish European inflammatory bowel disease-families).A nonsynonymous coding single nucleotide polymorphism in MORC4,located on the same linkage block as CLDN2,was investigated for association,as were two novel CLDN2 single nucleotide polymorphism markers,identified by resequencing.RESULTS:A single nucleotide polymorphism marker(rs12014762)located in the genetic region of CLDN2 was significantly associated to CD(case-control allelic OR = 1.98,95%CI:1.17-3.35,P = 0.007).MORC4 was present on the same linkage block as this CD marker.Using the case-control approach,a significant association(case control allelic OR = 1.61,95%CI:1.08-2.41,P = 0.018)was found between CD and a nonsynonymous coding single nucleotide polymorphism(rs6622126)in MORC4.The association between the CLDN2 marker and CD was not replicated in the familybased study.Ulcerative colitis was not associated to any of the single nucleotide polymorphism markers.CONCLUSION:These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.
文摘rs6311 and rs6313 are two Single Nucleotide Polymorphisms (SNPs) on the Serotonin Receptor 2A gene (5-HTR2A) in complete linkage disequilibrium. Numerous gene association studies have examined the relationships between one or both of these two polymorphisms and Major Depressive Disorder (MDD), with conflicting results. The present meta-analysis examined 19 case-control gene association studies, 9 of which included rs6311 (n = 3382), and 15 of which included rs6313 (n = 5590). The strength of relationship with MDD was assessed by pooled odds ratios and 95% confidence intervals for both SNPs according to four genetic models. Heterogeneity was measured by Q and I<sup>2</sup>. Subgrouping was performed by minor allele and by ethnicity. Results were nonsignificant for all models and subgroups, suggesting that genotype alone does not play a major role in genetic susceptibility to depression. The potential for epistatic, epigenetic, and regulatory RNA interactions with these SNPs is discussed, and future areas of research are recommended.
基金Supported by A Grant-in-Aid for Scientific Research from the Japanese Ministry of Education,Culture,Sports,Science and Technology
文摘Gastric cancer is the most common malignancy of the gastrointestinal tract in East Asian populations and the second most frequent cause of cancer-related mortality in the world. While previous studies have investigated the genetic factors involved in gastric carcinogenesis, there still exist relatively few studies that have investigated the genetic traits associated with the risk of gastric precancerous conditions. In this paper we will review the biology and genetic polymorphisms involved in the genesis of gastric precancerous conditions reported to date and discuss the future prospects of this field of study. The associations of gastric precancerous conditions with polymorphisms in the cytotoxin-associated gene A-related genes (e.g. PTPN11 G/A at intron 3, rs2301756), those in the genes involved in host immunity against Helico-bacter pylori (H. pylori) infection (e.g.TLR4 +3725G/C, rs11536889) or polymorphisms of the genes essential for the development/ differentiation of the gastric epithelial cells (e.g. RUNX3 T/A polymorphism at intron 3, rs760805) have been reported to date. Genetic epide-miological studies of the associations between H. pylori-induced gastric precancerous conditions and other gene polymorphisms in these pathways as well as polymor-phisms of the genes involved in other pathways like oxidative DNA damage repair pathways would provide useful evidence for the individualized prevention of these H. pylori-induced gastric precancerous conditions.
基金Supported by SCB is supported by a contract from the Fondo de Investigación Sanitaria,No.CP 03-0070CEJ and JM are supported by a contract from CIBERehd+7 种基金CIBERehd and CIB-ERER are funded by the Instituto de Salud Carlos IIIFondo de Investigación Sanitaria/FEDER,No.11/00219 and No.11/00681Instituto de Salud Carlos III(Acción Transversal de Cáncer),Xunta de Galicia,No.07PXIB9101209PRMinisterio de Cien-cia e Innovación,No.SAF2010-19273Asociación Espaola contra el Cáncer(Fundación Científica GCB13131592CAST y Junta de Barcelona)FundacióOlga Torres(SCB and CRP)FP7 CHIBCHA Consortium(SCB and ACar)COST Action BM1206(SCB and CRP)
文摘Colorectal cancer(CRC)is one of the most frequent neoplasms and an important cause of mortality in the developed world.This cancer is caused by both genetic and environmental factors although 35%of the variation in CRC susceptibility involves inherited genetic differences.Mendelian syndromes account for about5%of the total burden of CRC,with Lynch syndrome and familial adenomatous polyposis the most common forms.Excluding hereditary forms,there is an important fraction of CRC cases that present familial aggregation for the disease with an unknown germline genetic cause.CRC can be also considered as a complex disease taking into account the common diseasecommom variant hypothesis with a polygenic model of inheritance where the genetic components of common complex diseases correspond mostly to variants of low/moderate effect.So far,30 common,low-penetrance susceptibility variants have been identified for CRC.Recently,new sequencing technologies including exomeand whole-genome sequencing have permitted to add a new approach to facilitate the identification of new genes responsible for human disease predisposition.By using whole-genome sequencing,germline mutations in the POLE and POLD1 genes have been found to be responsible for a new form of CRC genetic predisposition called polymerase proofreading-associated polyposis.
