AIM: To validate novel single nucleotide polymorphisms (SNPs) in Greek patients with Crohn's disease (CD).METHODS: A total of 120 patients with CD, 85 patients with UC, and 100 unrelated healthy controls were geno...AIM: To validate novel single nucleotide polymorphisms (SNPs) in Greek patients with Crohn's disease (CD).METHODS: A total of 120 patients with CD, 85 patients with UC, and 100 unrelated healthy controls were genotyped. Genotyping was performed by allele-specific PCR or by PCR-RFLP analysis.RESULTS: Our results showed that the 1672T and -207C alleles were obviously over-represented in CD patients only (P＜0.01 and P＜0.05, respectively) compared to the control population. The G113A polymorphism was completely absent in our studied population. The odds ratio for the carriage of the TC haplotype was 2.21 for CD patients as compared with controls. Additionally, the frequency of the TC haplotype was increased in patients with ileocolitis or colitis, and was mainly associated with the fibrostenotic phenotype of the disease. Furthermore, when the TC haplotype was compared jointly with the carriage of at least one mutation of the NOD2/CARD15 gene, there was an increased risk for CD, but not for UC, compared to controls. Regarding the location of the disease, the concomitant presence of the TC haplotype and NOD2/CARD15 mutations was mainly associated with ileocolitis or ileitis. CONCLUSION: Collectively, our results suggest that the 1672T variant of the OCTN1 gene and the -207C variant of the OCTN2 gene represent risk factors for CD in the Greek population.展开更多
Background and aims:The OCTN1(SLC22A4 1672C→ T) and OCTN2(SLC22A5-207G→ C) variants within the IBD5 locus have been associated with susceptibility to adult onset Crohn’s disease(CD) ,but their contribution in child...Background and aims:The OCTN1(SLC22A4 1672C→ T) and OCTN2(SLC22A5-207G→ C) variants within the IBD5 locus have been associated with susceptibility to adult onset Crohn’s disease(CD) ,but their contribution in children has not been examined.Methods:These OCTN1/2 variants and IBD5 marker single nucleotide polymorphisms(SNPs) (IGR2096a-1,IGR2198a-1,and IGR2230a-1) were examined in 299 Scottish children(200 with CD,74 with ulcerative colitis(UC) ,and 25 with indeterminate colitis(IC) ) ,together with 502 parents(for transmission disequilibrium testing) and 250 controls.Results:All SNPs were in strong linkage disequilibrium(D’ >0.94) .TDT analysis showed association of the OCTN1 variant with inflammatory bowel disease(IBD) (p = 0.01) and CD(p = 0.04) .Allele frequencies of the OCTN1/2 variants were significantly higher in IBD/CD cases(p < 0.04) .The homozygous mutant OCTN1/2 haplotype was increased in IBD(24.3% v 16.1%,p = 0.02) and UC(28.2% v 16.1%,p = 0.02) compared with controls.The OCTN1/2 variants were not independent of the background IBD5 risk haplotype in conferring disease susceptibility.Unifactorial analysis in CD patients showed that carriage of the TC haplotype was associated with lower weight,height,and BMI centile(< 9th centile) at diagnosis(weight:87.9% v 67.3%(p = 0.002) ,odds ratio(OR) = 3.52(95% confidence interval,1.51 to 8.22) ;height:84.1% v 68.4%(p< 0.05) ,OR = 2.44(1.00 to 5.99) ;BMI:79.6% v 61.1%(p = 0.02) ,OR = 2.49(1.14 to 5.44) ) ,and lower weight centile at follow up(87.5% v 64.6%(p = 0.03) ,OR = 3.83(1.03 to 14.24) ) .Multifactorial binary logistic regression analysis confirmed association of the TC haplotype with lower weight centile at diagnosis(p = 0.02,OR = 3.41(1.20 to 9.66) ) .Conclusions:These data implicate variants within the IBD5 haplotype,as determinants of disease susceptibility and growth indices in early onset IBD.The OCTN1/2 variants remain potential positional candidate genes,but require further analysis.展开更多
AIM： To investigate the frequency of the common NOD2/CARD15 susceptibility variants and two functional polymorphisms of OCTN cation transporter genes in Hungarian pediatric patients with Crohn＇s disease （CD）. METH...AIM： To investigate the frequency of the common NOD2/CARD15 susceptibility variants and two functional polymorphisms of OCTN cation transporter genes in Hungarian pediatric patients with Crohn＇s disease （CD）. METHODS： A cohort of 19 unrelated pediatric and 55 unrelated adult patients with Crohn＇s disease and 49 healthy controls were studied. Genotyping of the three common CD-associated CARD15 variants （Arg702Trp, Gly908Arg and 2007finsC changes） with the SLC22A4 1672C→T, and SLC22A5 -207G→C mutations was performed by direct sequencing of the specific regions of these genes. RESULTS： At least one CARD15 mutation was present in 52.6% of the children and in 34.5% of the adults compared to 14.3% in controls. Surprisingly, strongly different mutation profile was detected in the pediatric versus adult patients. While the G908R and 1007finsC variants were 18.4% and 21.1% in the pediatric group, they were 1.82% and 11.8% in the adults, and were 1.02% and 3.06% in the controls, respectively. The R702W allele was increased approximately two-fold in the adult subjects, while in the pediatric group it was only approximately 64% of the controls （9.09% in the adults, 2.63% in pediatric patients, and 4.08% in the controls）. No accumulation of the OCTN variants was observed in any patient group versus the controls.CONCLUSION： The frequency of the NOD2/CARD15 susceptibility variants in the Hungarian pediatric CD population is high and the profile differs from the adult CD patients, whereas the results for SLC22A4 and SLC22A5 mutation screening do not confirm the assumption that the carriage of these genotypes means an obligatory susceptibility to CD.展开更多
A novel selenium-containing compound,selenoneine,has been isolated as the major form of organic selenium in the blood and tissues of tuna.Selenoneine harbors a selenium atom in the imidazole ring,2-selenylNα,Nα,Nα-...A novel selenium-containing compound,selenoneine,has been isolated as the major form of organic selenium in the blood and tissues of tuna.Selenoneine harbors a selenium atom in the imidazole ring,2-selenylNα,Nα,Nα-trimethyl-L-histidine,and is a selenium analog of ergothioneine.This selenium compound has strong antioxidant capacity and binds to heme proteins,such as hemoglobin and myoglobin,to protect them from iron auto-oxidation,and it reacts with radicals and methylmercury(MeHg) .The organic cations/carnitine transporter OCTN1 transports selenoneine and MeHg,regulates Se-enhanced antioxidant activity,and decreases MeHg toxicity.Thus,the dietary intake of selenoneine,by consuming fish,might decrease the formation of reactive oxygen radicals that could oxidize nucleotides in DNA,and thereby inhibit carcinogenesis,chronic diseases,and aging.展开更多
文摘AIM: To validate novel single nucleotide polymorphisms (SNPs) in Greek patients with Crohn's disease (CD).METHODS: A total of 120 patients with CD, 85 patients with UC, and 100 unrelated healthy controls were genotyped. Genotyping was performed by allele-specific PCR or by PCR-RFLP analysis.RESULTS: Our results showed that the 1672T and -207C alleles were obviously over-represented in CD patients only (P＜0.01 and P＜0.05, respectively) compared to the control population. The G113A polymorphism was completely absent in our studied population. The odds ratio for the carriage of the TC haplotype was 2.21 for CD patients as compared with controls. Additionally, the frequency of the TC haplotype was increased in patients with ileocolitis or colitis, and was mainly associated with the fibrostenotic phenotype of the disease. Furthermore, when the TC haplotype was compared jointly with the carriage of at least one mutation of the NOD2/CARD15 gene, there was an increased risk for CD, but not for UC, compared to controls. Regarding the location of the disease, the concomitant presence of the TC haplotype and NOD2/CARD15 mutations was mainly associated with ileocolitis or ileitis. CONCLUSION: Collectively, our results suggest that the 1672T variant of the OCTN1 gene and the -207C variant of the OCTN2 gene represent risk factors for CD in the Greek population.
文摘Background and aims:The OCTN1(SLC22A4 1672C→ T) and OCTN2(SLC22A5-207G→ C) variants within the IBD5 locus have been associated with susceptibility to adult onset Crohn’s disease(CD) ,but their contribution in children has not been examined.Methods:These OCTN1/2 variants and IBD5 marker single nucleotide polymorphisms(SNPs) (IGR2096a-1,IGR2198a-1,and IGR2230a-1) were examined in 299 Scottish children(200 with CD,74 with ulcerative colitis(UC) ,and 25 with indeterminate colitis(IC) ) ,together with 502 parents(for transmission disequilibrium testing) and 250 controls.Results:All SNPs were in strong linkage disequilibrium(D’ >0.94) .TDT analysis showed association of the OCTN1 variant with inflammatory bowel disease(IBD) (p = 0.01) and CD(p = 0.04) .Allele frequencies of the OCTN1/2 variants were significantly higher in IBD/CD cases(p < 0.04) .The homozygous mutant OCTN1/2 haplotype was increased in IBD(24.3% v 16.1%,p = 0.02) and UC(28.2% v 16.1%,p = 0.02) compared with controls.The OCTN1/2 variants were not independent of the background IBD5 risk haplotype in conferring disease susceptibility.Unifactorial analysis in CD patients showed that carriage of the TC haplotype was associated with lower weight,height,and BMI centile(< 9th centile) at diagnosis(weight:87.9% v 67.3%(p = 0.002) ,odds ratio(OR) = 3.52(95% confidence interval,1.51 to 8.22) ;height:84.1% v 68.4%(p< 0.05) ,OR = 2.44(1.00 to 5.99) ;BMI:79.6% v 61.1%(p = 0.02) ,OR = 2.49(1.14 to 5.44) ) ,and lower weight centile at follow up(87.5% v 64.6%(p = 0.03) ,OR = 3.83(1.03 to 14.24) ) .Multifactorial binary logistic regression analysis confirmed association of the TC haplotype with lower weight centile at diagnosis(p = 0.02,OR = 3.41(1.20 to 9.66) ) .Conclusions:These data implicate variants within the IBD5 haplotype,as determinants of disease susceptibility and growth indices in early onset IBD.The OCTN1/2 variants remain potential positional candidate genes,but require further analysis.
基金Supported by the grant of Hungarian Science Foundation No. OTKA T 49589
文摘AIM： To investigate the frequency of the common NOD2/CARD15 susceptibility variants and two functional polymorphisms of OCTN cation transporter genes in Hungarian pediatric patients with Crohn＇s disease （CD）. METHODS： A cohort of 19 unrelated pediatric and 55 unrelated adult patients with Crohn＇s disease and 49 healthy controls were studied. Genotyping of the three common CD-associated CARD15 variants （Arg702Trp, Gly908Arg and 2007finsC changes） with the SLC22A4 1672C→T, and SLC22A5 -207G→C mutations was performed by direct sequencing of the specific regions of these genes. RESULTS： At least one CARD15 mutation was present in 52.6% of the children and in 34.5% of the adults compared to 14.3% in controls. Surprisingly, strongly different mutation profile was detected in the pediatric versus adult patients. While the G908R and 1007finsC variants were 18.4% and 21.1% in the pediatric group, they were 1.82% and 11.8% in the adults, and were 1.02% and 3.06% in the controls, respectively. The R702W allele was increased approximately two-fold in the adult subjects, while in the pediatric group it was only approximately 64% of the controls （9.09% in the adults, 2.63% in pediatric patients, and 4.08% in the controls）. No accumulation of the OCTN variants was observed in any patient group versus the controls.CONCLUSION： The frequency of the NOD2/CARD15 susceptibility variants in the Hungarian pediatric CD population is high and the profile differs from the adult CD patients, whereas the results for SLC22A4 and SLC22A5 mutation screening do not confirm the assumption that the carriage of these genotypes means an obligatory susceptibility to CD.
基金Supported by In part grants from the Ministry of Agriculture,Forestry,and Fisheries of Japan(Rural Biomass Research Project,BM-D2300)and Fisheries Research Agency
文摘A novel selenium-containing compound,selenoneine,has been isolated as the major form of organic selenium in the blood and tissues of tuna.Selenoneine harbors a selenium atom in the imidazole ring,2-selenylNα,Nα,Nα-trimethyl-L-histidine,and is a selenium analog of ergothioneine.This selenium compound has strong antioxidant capacity and binds to heme proteins,such as hemoglobin and myoglobin,to protect them from iron auto-oxidation,and it reacts with radicals and methylmercury(MeHg) .The organic cations/carnitine transporter OCTN1 transports selenoneine and MeHg,regulates Se-enhanced antioxidant activity,and decreases MeHg toxicity.Thus,the dietary intake of selenoneine,by consuming fish,might decrease the formation of reactive oxygen radicals that could oxidize nucleotides in DNA,and thereby inhibit carcinogenesis,chronic diseases,and aging.
