AIM： TO estimate the prevalence of the lactase non-persistent genotype （C/C-23910） in a northern Russian population in accordance with ethnicity, and to evaluate self-reported milk consumption depending on lactase ...AIM： TO estimate the prevalence of the lactase non-persistent genotype （C/C-23910） in a northern Russian population in accordance with ethnicity, and to evaluate self-reported milk consumption depending on lactase activity. METHODS： Blood samples for genotyping lactase activity, defining the C/T-13910 variant by polymerase chain reaction, and direct sequencing were taken from 231 medical students of Russian origin aged 17-26 years. We analyzed milk product consumption by questionnaire which was specially designed for the estimation of milk consumption and abdominal complaints. RESULTS： We found that the prevalence of the C/C-13190 genotype in the northern Russian population was 35.6%. The other genotypes nearby C/T-13910 and associated with lactase activity were not present in the study population. The consumption of milk among people with the non-persistent genotype tended to be lower than among the lactose tolerant subjects, but was not statistically significant. CONCLUSION： An investigation of the lactase persistent genotype in a northern Russian population has not been performed before, The genotype did not affect the consumption of milk products in this population which could be explained by low consumption of milk products among the entire study population.展开更多
AIM:To analyze the epidermal growth factor receptor pathway substrate 8(EPS8) expression status and role in colorectal carcinogenesis given that EPS8 has a conserved actin barbed-end capping function that is required ...AIM:To analyze the epidermal growth factor receptor pathway substrate 8(EPS8) expression status and role in colorectal carcinogenesis given that EPS8 has a conserved actin barbed-end capping function that is required for proper maturation in intestinal cells.METHODS:We studied 8 colon cancer cell lines and 58 colorectal tumors(19 adenomas and 39 carcinomas).We performed expression microarray analysis of colon cancer cell lines followed by loss of heterozygosity(LOH)analysis and immunohistochemistry for EPS8 expression in colon tumors.Subsequently,we performed mutation analysis by direct sequencing and methylation analysis by bisulfite sequencing and methylation-specific polymerase chain reaction assays.RESULTS:Expression microarray analysis of colon cancer cell lines showed overexpression of EPS8 transcript in all lines but RKO.Genome wide loss of heterozygosity(LOH) analysis of colon tumors,showed considerable LOH at the EPS8 gene locus.Immunohistochemically,EPS8 was constitutively expressed in normal colonic mucosa with a dot-like supranuclear localization with accentuation at the luminal surface supporting its proposed role in epithelial maturation.Nineteen colon tumors(4 adenoma,15 carcinoma) out of 51(37%) showed strikingly tumor specific EPS8 protein loss.Of the remaining tumors,5/51(2 adenoma,and 3 carcinoma,10%) showed marked overexpression,while 27/51 tumors(53%) showed retained expression.Mutation analysis revealed a missense mutation(c.794C>T,p.R265C) in exon 8 in RKO.The EPS8 promoter was also methylated in RKO,but there was no significant methylation in other cell lines or carcinoma specimens.CONCLUSION:The loss of EPS8 expression in colorectal adenomas and carcinomas suggests that down regulation of this gene contributes to the development of a subset of colorectal cancers,a finding which could have applications in diagnosis and treatment.展开更多
AIM： To assess the role of lactase non-persistence/per- sistence in school-aged children and their milk-related symptoms. METHODS： The genotypes for the C/T-13910 variant associated with lactase non-persistence/ per...AIM： To assess the role of lactase non-persistence/per- sistence in school-aged children and their milk-related symptoms. METHODS： The genotypes for the C/T-13910 variant associated with lactase non-persistence/ persistence were determined using PCR-minisequencing in a group of 172 children with a mean age of 8.6 years （SE = 0.02, 93 boys） participating in a follow-up study for cow＇s milk allergy. The parents were asked to assess their children＇s milk consumption and abdominal symptoms. RESULTS： The presence of allergy to cow＇s milk was not associated with the C/C-13910 genotype related with a decline of lactase enzyme activity during childhood （lactase non-persistence）. The frequency of the C/C-13910 genotype （16%） was similar to published figures for the prevalence of adult-type hypolactasia in Finland. The majority of the children （90%） in this series consumed milk but 26% of their families suspected that their children had milk-related symptoms. Forty-eight percent of the children with the C/C-13910 genotype did not drink milk at all or consumed a low lactose containing diet prior to the genotyping （P〈 0.004 when compared to the other genotypes）. CONCLUSION： Analysis of the C/T-13910 polymorphism is an easy and reliable method for excluding adult-type hypolactasia in children with milk-related symptoms. Genotyping for this variant can be used to advise diets for children with a previous history of cow＇s milk allergy.展开更多
AIM： To correlate the C/T-13910 variant, associated with lactase persistence/non-persistence （adulttype hypolactasia） trait, with intestinal disaccharidase activities in different age groups of the adult population...AIM： To correlate the C/T-13910 variant, associated with lactase persistence/non-persistence （adulttype hypolactasia） trait, with intestinal disaccharidase activities in different age groups of the adult population.METHODS： Intestinal biopsies were obtained from 222 adults aged 18 to 83 years undergoing upper gastrointestinal endoscopy because of unspecified abdominal complaints. The biopsies were assayed for lactase, sucrase and maltase activities and genotyped for the C/T-13910 variant using PCR-minisequencing. RESULTS： There was a significant correlation between lactase activity and the C/T-13910 variant （P 〈 0.00001）. The mean level of lactase activity among subjects with C/C-1391o genotype was 6.86± 0.35 U/g, with C/T-13910 genotype 37.8 ± 1.4 U/g, and with T/T-13910 genotype 57.6± 2.4 U/g protein, showing a trimodal distribution of this enzyme activity. Significant differences were also observed in maltase activities among individuals with different C/T-13910 genotypes （P = 0.005）. In contrast, in sucrase activity, no significant differences emerged between the C/T-13910 genotypes （P = 0.14）. There were no statistical differences in lactase （P = 0.84）, sucrase （P = 0.18）, or maltase activity （P = 0.24） among different age groups. In the majority （〉 84%） of the patients with the C/C-13910 genotype associated with lactase non- persistence, the lactase activity was less than 10 U/g protein.CONCLUSION： Our study demonstrates a statistically significant correlation between the C/T-13910 genotype and lactase activity and this correlation is not affected by age in adults but the cut-off value of 20 U/g protein used for the diagnosis of lactase non-persistence might be too high.展开更多
AIM: To study milk consumption and subjective milk- related symptoms in adults genotyped for adult-type hypolactasia. METHODS: A total of 1900 Finnish adults were genotyped for the C/T-13910 variant of adult-type hypo...AIM: To study milk consumption and subjective milk- related symptoms in adults genotyped for adult-type hypolactasia. METHODS: A total of 1900 Finnish adults were genotyped for the C/T-13910 variant of adult-type hypolactasia and filled in a structured questionnaire concerning milk consumption and gastrointestinal problems. RESULTS: The C/C-13910 genotype of adult-type hypolactasia was present in 18% of the study population. The prevalence of the C/C-13910 genotype was higher among subjects who were undergoing investigations because of abdominal symptoms (24%, P < 0.05). Those with the C/C-13910 genotype drank less milk than subjects with either the C/T-13910 or the T/T-13910 genotype of lactase persistence (18% vs 38%; 18% vs 36%, P < 0.01). Subjects with the C/C-13910 genotype had experienced more gastrointestinal symptoms (84%) during the preceding three-month period than those with the C/T-13910 (79%, P < 0.05) or the T/T-13910 genotype (78 %, P < 0.05). Only 9% (29/338) of the subjects with the C/C-13910 genotype consumed milk and reported no symptoms from it.CONCLUSION: Gastrointestinal symptoms are more common among adults with the C/C-13910 genotype of adult-type hypolactasia than in those with genotypes of lactase persistence.展开更多
AIM： To define the frequency of the cfr-13910 variant associated with lactase persistence/non-persistence trait and to analyze the milk consumption of lactase non- persistent subjects in Estonia. METHODS： We genotyp...AIM： To define the frequency of the cfr-13910 variant associated with lactase persistence/non-persistence trait and to analyze the milk consumption of lactase non- persistent subjects in Estonia. METHODS： We genotyped 355 Estonians by polymerase chain reaction and direct sequencing, Milk consumption was analyzed by a questionnaire, specially developed to analyze milk consumption and abdominal complaints. RESULTS： The frequency of the genotype of the C/ C-13910 （lactase non-persistence） was found to be 24.8% in native Estonians. No other single nucleotide polymorphisms covering the region of 400 bp adjacent to the C/T-13910 variant were found. Lactase non- persistence subjects were found to consume less milk than lactase persistence subjects. CONCLUSION： The frequency of lactase non- persistence defined by the C/C-13910 genotype confirms the results of the previous studies based on indirect methods of determining hypolactasia, Milk consumption of lactase non-persistence subjects is consistent with previously reported figures of adult-type hypolactasia in Estonia, However, lactase non-persistence does not prevent the intake of milk in many adults.展开更多
基金The Sigrid Jusélius Foundation,Helsinki,Finland and Tampere University Hospital Research Funds
文摘AIM： TO estimate the prevalence of the lactase non-persistent genotype （C/C-23910） in a northern Russian population in accordance with ethnicity, and to evaluate self-reported milk consumption depending on lactase activity. METHODS： Blood samples for genotyping lactase activity, defining the C/T-13910 variant by polymerase chain reaction, and direct sequencing were taken from 231 medical students of Russian origin aged 17-26 years. We analyzed milk product consumption by questionnaire which was specially designed for the estimation of milk consumption and abdominal complaints. RESULTS： We found that the prevalence of the C/C-13190 genotype in the northern Russian population was 35.6%. The other genotypes nearby C/T-13910 and associated with lactase activity were not present in the study population. The consumption of milk among people with the non-persistent genotype tended to be lower than among the lactose tolerant subjects, but was not statistically significant. CONCLUSION： An investigation of the lactase persistent genotype in a northern Russian population has not been performed before, The genotype did not affect the consumption of milk products in this population which could be explained by low consumption of milk products among the entire study population.
基金Supported by The Academy of Finlandigrid Juselius Foundation+4 种基金University of SharjahTerry Fox FundFinnish Cancer FoundationBiocentrum Helsinkithe European Research Council
文摘AIM:To analyze the epidermal growth factor receptor pathway substrate 8(EPS8) expression status and role in colorectal carcinogenesis given that EPS8 has a conserved actin barbed-end capping function that is required for proper maturation in intestinal cells.METHODS:We studied 8 colon cancer cell lines and 58 colorectal tumors(19 adenomas and 39 carcinomas).We performed expression microarray analysis of colon cancer cell lines followed by loss of heterozygosity(LOH)analysis and immunohistochemistry for EPS8 expression in colon tumors.Subsequently,we performed mutation analysis by direct sequencing and methylation analysis by bisulfite sequencing and methylation-specific polymerase chain reaction assays.RESULTS:Expression microarray analysis of colon cancer cell lines showed overexpression of EPS8 transcript in all lines but RKO.Genome wide loss of heterozygosity(LOH) analysis of colon tumors,showed considerable LOH at the EPS8 gene locus.Immunohistochemically,EPS8 was constitutively expressed in normal colonic mucosa with a dot-like supranuclear localization with accentuation at the luminal surface supporting its proposed role in epithelial maturation.Nineteen colon tumors(4 adenoma,15 carcinoma) out of 51(37%) showed strikingly tumor specific EPS8 protein loss.Of the remaining tumors,5/51(2 adenoma,and 3 carcinoma,10%) showed marked overexpression,while 27/51 tumors(53%) showed retained expression.Mutation analysis revealed a missense mutation(c.794C>T,p.R265C) in exon 8 in RKO.The EPS8 promoter was also methylated in RKO,but there was no significant methylation in other cell lines or carcinoma specimens.CONCLUSION:The loss of EPS8 expression in colorectal adenomas and carcinomas suggests that down regulation of this gene contributes to the development of a subset of colorectal cancers,a finding which could have applications in diagnosis and treatment.
基金Supported by The Sigrid Juselius Foundation, Helsinki, Finland The Helsinki University Hospital Research Funding, Helsinki, Finland The Helsinki University Science Foundation, Helsinki, Finland and The Foundation of Nutrition Research, Helsinki, Finland
文摘AIM： To assess the role of lactase non-persistence/per- sistence in school-aged children and their milk-related symptoms. METHODS： The genotypes for the C/T-13910 variant associated with lactase non-persistence/ persistence were determined using PCR-minisequencing in a group of 172 children with a mean age of 8.6 years （SE = 0.02, 93 boys） participating in a follow-up study for cow＇s milk allergy. The parents were asked to assess their children＇s milk consumption and abdominal symptoms. RESULTS： The presence of allergy to cow＇s milk was not associated with the C/C-13910 genotype related with a decline of lactase enzyme activity during childhood （lactase non-persistence）. The frequency of the C/C-13910 genotype （16%） was similar to published figures for the prevalence of adult-type hypolactasia in Finland. The majority of the children （90%） in this series consumed milk but 26% of their families suspected that their children had milk-related symptoms. Forty-eight percent of the children with the C/C-13910 genotype did not drink milk at all or consumed a low lactose containing diet prior to the genotyping （P〈 0.004 when compared to the other genotypes）. CONCLUSION： Analysis of the C/T-13910 polymorphism is an easy and reliable method for excluding adult-type hypolactasia in children with milk-related symptoms. Genotyping for this variant can be used to advise diets for children with a previous history of cow＇s milk allergy.
基金a grant from the Emil Aaltonen Foundation, Tampere, the Sigrid Jusélius Foundation, Helsinki, the Center of Excellence in Disease Genetics of the Academy of Finland, Helsinki University Research Funding, Helsinki, and Finnish Cultural Foundation, Helsinki, Finland
文摘AIM： To correlate the C/T-13910 variant, associated with lactase persistence/non-persistence （adulttype hypolactasia） trait, with intestinal disaccharidase activities in different age groups of the adult population.METHODS： Intestinal biopsies were obtained from 222 adults aged 18 to 83 years undergoing upper gastrointestinal endoscopy because of unspecified abdominal complaints. The biopsies were assayed for lactase, sucrase and maltase activities and genotyped for the C/T-13910 variant using PCR-minisequencing. RESULTS： There was a significant correlation between lactase activity and the C/T-13910 variant （P 〈 0.00001）. The mean level of lactase activity among subjects with C/C-1391o genotype was 6.86± 0.35 U/g, with C/T-13910 genotype 37.8 ± 1.4 U/g, and with T/T-13910 genotype 57.6± 2.4 U/g protein, showing a trimodal distribution of this enzyme activity. Significant differences were also observed in maltase activities among individuals with different C/T-13910 genotypes （P = 0.005）. In contrast, in sucrase activity, no significant differences emerged between the C/T-13910 genotypes （P = 0.14）. There were no statistical differences in lactase （P = 0.84）, sucrase （P = 0.18）, or maltase activity （P = 0.24） among different age groups. In the majority （〉 84%） of the patients with the C/C-13910 genotype associated with lactase non- persistence, the lactase activity was less than 10 U/g protein.CONCLUSION： Our study demonstrates a statistically significant correlation between the C/T-13910 genotype and lactase activity and this correlation is not affected by age in adults but the cut-off value of 20 U/g protein used for the diagnosis of lactase non-persistence might be too high.
基金the Sigrid Jusélius Foundation, Helsinki, Finlandthe Foundation for Nutrition Research, Helsinki, Finland+3 种基金the Research Foundation of Alfred Kordelin, Helsinki, FinlandHelsinki University Hospital Research Funding, Helsinki, Finlandthe Foundation for Promoting Occupational Medicine in Finland,Helsinki,Finlandthe Academy of Finland
文摘AIM: To study milk consumption and subjective milk- related symptoms in adults genotyped for adult-type hypolactasia. METHODS: A total of 1900 Finnish adults were genotyped for the C/T-13910 variant of adult-type hypolactasia and filled in a structured questionnaire concerning milk consumption and gastrointestinal problems. RESULTS: The C/C-13910 genotype of adult-type hypolactasia was present in 18% of the study population. The prevalence of the C/C-13910 genotype was higher among subjects who were undergoing investigations because of abdominal symptoms (24%, P < 0.05). Those with the C/C-13910 genotype drank less milk than subjects with either the C/T-13910 or the T/T-13910 genotype of lactase persistence (18% vs 38%; 18% vs 36%, P < 0.01). Subjects with the C/C-13910 genotype had experienced more gastrointestinal symptoms (84%) during the preceding three-month period than those with the C/T-13910 (79%, P < 0.05) or the T/T-13910 genotype (78 %, P < 0.05). Only 9% (29/338) of the subjects with the C/C-13910 genotype consumed milk and reported no symptoms from it.CONCLUSION: Gastrointestinal symptoms are more common among adults with the C/C-13910 genotype of adult-type hypolactasia than in those with genotypes of lactase persistence.
基金Supported by the Estonian Science Foundation grant No. 6452, Sigrid Jusélius Foundation, Helsinki, Finland and Helsinki University Hospital Research Funding, University of Helsinki, Finland
文摘AIM： To define the frequency of the cfr-13910 variant associated with lactase persistence/non-persistence trait and to analyze the milk consumption of lactase non- persistent subjects in Estonia. METHODS： We genotyped 355 Estonians by polymerase chain reaction and direct sequencing, Milk consumption was analyzed by a questionnaire, specially developed to analyze milk consumption and abdominal complaints. RESULTS： The frequency of the genotype of the C/ C-13910 （lactase non-persistence） was found to be 24.8% in native Estonians. No other single nucleotide polymorphisms covering the region of 400 bp adjacent to the C/T-13910 variant were found. Lactase non- persistence subjects were found to consume less milk than lactase persistence subjects. CONCLUSION： The frequency of lactase non- persistence defined by the C/C-13910 genotype confirms the results of the previous studies based on indirect methods of determining hypolactasia, Milk consumption of lactase non-persistence subjects is consistent with previously reported figures of adult-type hypolactasia in Estonia, However, lactase non-persistence does not prevent the intake of milk in many adults.
