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Genetic Variation in the Human Interleukin 4 (Il4) Gene is Associated With Gallstone Susceptibility
and transfatty acid intake, adjusted for known risk factors: age, body mass index, energy, alcohol and physical activity in men, and also parity and hormone replacement therapy use in women. Results: 177 women (mean age of diagnosis 66.5yrs SD=9.5yrs) and 90 men (64.2yrs S.D=9.2yrs) developed symptomatic gallstones. In women, increased dietary cholesterol was associated with a decreased risk of disease (highest vs lowest fifth, HR=0.52 95% CI=0.31-0.86, per fifth increase HR=0.83 95% CI=0.74-0.93, p for trend=0.002), with no effect in men (trend across fifths HR=0.92 95% CI=0.78-1.08). Increased transfatty acid intake in women increased the risk of disease (highest vs lowest fifth HR=2.18 95% CI= 1.21-3.92, per fifth increase HR=1.17 95% CI=1.02-1.35, p for trend=0.023), with no effect in men (trend across fifths HR=1.01 95% CI=0.84-1.23). Conclusion: In women, low dietary cholesterol and high transfatty acid intake increased the risk of developing symptomatic gallstones, for which there are plausible biological mechanisms. No effects were found in men, though this could be due to a lack of power with only half the number of cases diagnosed. Dietary cholesterol and transfatty acids should be measured in future aetiological studies of gallstones. Risk of developing symptomatic gallstones by fifths of dietary cholesterol and transfatty acid intake in women and men.
Su1274 Dietary Deficiencies of Iron and Niacin in the Aetiology of Symptomatic Gallstones - Data From a UK Prospective Cohort Study (EPIC-Norfolk) Using 7-Day Food Diaries Paul R. Banim, Robert Luben, Kay-Tee Khaw, Stephen J. Sharp, Nick Wareham, Andrew Hart Introduction: Low iron intake reduces nitric oxide synthase (NOS) activity, which impairs gallbladder motility and bile flow. Low iron intake decreases activity of cholesterol 7-αhydroxlase, an enzyme which converts cholesterol to bile acids. Niacin increases plasma high density lipoprotein and lowers plasma triglycerides, both of which are associated with a lower incidence of gallstone disease. This study investigated dietary iron and niacin intake and the risk of developing symptomatic gallstones, for the first time using seven-day food diaries (7-DFDs), the most accurate feasible method of estimating food intake in large epidemiological studies. Methods: 25 639 participants (56% women), aged 40-74 yrs were recruited into the European Prospective Investigation into Cancer-Norfolk (EPIC-Norfolk) with 23 658 completing 7-DFDs at enrolment. The cohort was monitored for 14 years for new symptomatic gallstones, with diagnoses confirmed by review of the clinical notes. The 7-DFDs recorded one week's diet including food types, frequency of consumption, quantities and cooking methods. A representative sample of 3 970 and those with gallstone disease had their 7-DFDs coded by nutritionists using a computer program containing nutrient information on 11 000 food and 55 000 portion sizes. A cohort analysis used Cox regression to estimate sex specific hazard ratios (HR) for developing gallstones comparing fifths of dietary iron and niacin acid intake adjusted for age, body mass index, energy, alcohol and physical activity in men, and also parity and hormone replacement therapy use in women. Results: 177 women (mean age of diagnosis 66.5yrs SD=9.5yrs) and 90 men (64.2yrs SD= 9.2yrs) developed symptomatic gallstones. In women, increased dietary iron intake was associated with a decreased risk of symptomatic gallstones (highest vs lowest fifth, HR=0.36 95% CI=0.20-0.66; per fifth increase, HR=0.82 95% CI=0.72-0.94 p=0.003), although no effects were seen in men (per fifth increase, HR=0.97 95% CI=0.81-1.17). Increased dietary niacin intake was also associated with a decreased risk of disease in women (highest vs lowest fifth, HR=0.50 95% CI=0.30-0.83; per fifth increase, HR=0.86 95% CI=0.76-0.97 p=0.011), but no effects were found in men (per fifth increase, HR=0.96 95% CI=0.811.14). Conclusion: In women, gallstone disease may be prevented by increasing dietary iron and niacin intake, for which there are plausible biological mechanisms. No effects were found in men, although this could be due to a lack of power as only half the number of cases diagnosed and also that men are less likely to be iron deficient. These nutrients should be measured in future studies to confirm the association. Risk of developing symptomatic gallstones by fifths of dietary intake of iron and niacin in women and men.
Decreased dietary cholesterol and increased dietary transfatty acids were associated with an increased risk of developing symptomatic gallstones. HR = Hazard ratio CI = confidence interval Analysis was adjusted for age, body mass index, energy, alcohol and physical acitivity in men with the addition of hormone replacement therapy and parity in women Su1276 Genetic Variation in the Human Interleukin 4 (Il4) Gene is Associated With Gallstone Susceptibility Anke Tönjes, Teresa Strauch, Claudia Ruffert, Joachim Mossner, Michael Stumvoll, Peter Kovacs, Henning Wittenburg Introduction: The individual risk to develop gallstones is determined by risk alleles of gallstone-susceptibility (LITH) genes and their interactions with environmental factors such as rapid weight loss, diet, and specific medications. Quantitative trait locus mapping in the inbred mouse model of cholesterol cholelithiasis identified a Lith locus on mouse chromosome 11, which co-localizes with the Il4 gene. In addition, ablation of Il4 promoted cholesterol gallstone formation in the mouse model of cholelithiasis rendering IL4 an interesting LITH candidate gene based on the presumed concordance of murine and human LITH genes. Methods: To systematically explore the IL4 gene as a LITH gene in humans, we performed a genetic association study in gallstone carriers (N = 184) and control subjects without evidence for gallstones (N = 833) from a self-contained population of Sorbs from Saxony. Based on the HapMap database, three haplotype-tagging single nucleotide polymorphisms (SNPs) (rs2243290, rs2227284 and rs2243263) capturing the genetic variation of IL4 (r2 cutoff 0.8; minor allele frequency > 0.05) were genotyped in cases and controls employing the TaqMan method. Data were analyzed in the additive model using logistic regression including age, sex and body mass index as covariates. The local ethics committee approved the study and all participants gave written informed consent. Results: Two of the three SNPs were associated with cholelithiasis, rs2243290 (P = 0.06) and rs2227284 (P = 0.02). In addition, when only cases with a previous history of a cholecystectomy were considered, both SNPs were significantly associated with symptomatic gallstone disease (rs2243290 (P = 0.009); rs2227284 (P = 0.002)). For both SNPs, an increase in gallstone susceptibility was associated with the variant minor allele. Conclusion: Our results indicate an increased gallstone risk from frequent variants of IL4. Anti-inflammatory mechanisms might explain a protective effect of IL4 on cholelithiasis by up-regulation of PPARγ and a reduction of leukotriene production by inhibition of the arachodinate-5-lipoxygenase. In turn, this might lead to a diminished production of mucin glycoproteins. Accordingly, our findings suggest that IL4 could be a target for prevention and non-surgical management of cholelithiasis in genetically predisposed patients.
Increased dietary iron and niacin intake is associated with a decreased risk of symptomatic gallstones in women. HR = Hazard Ratio CI = Confidence Interval Analysis was adjusted for age, body mass index, energy intake, alcohol intake and physical activity in men with the addition of hormone replacement therapy and parity in women. Su1275 The Role of Dietary Cholesterol and Transfatty Acids in the Aetiology of Gallstones. A UK Prospective Cohort Study (EPIC-Norfolk) Using 7-Day Food Diaries Paul R. Banim, Robert Luben, Stephen J. Sharp, Nick Wareham, Kay-Tee Khaw, Andrew Hart Introduction: Dietary cholesterol may prevent gallstone formation by up-regulating the enzyme cholesterol 7-α hydroxlase (Cyp7a1), which converts cholesterol to primary bile acids and prevents biliary cholesterol supersaturation, a prerequisite for cholesterol stone formation. Transfatty acids promote hyperinsulinaemia which inhibits Cyp7A1 and could promote gallstone disease. This study investigated dietary cholesterol and transfatty acid intake on the risk of developing symptomatic gallstones,for the first time using seven-day food diaries (7-DFDs), the most accurate feasible method of estimating food intake in large studies. Methods: 25 639 participants (56% women), aged 40-74 yrs were recruited into the European Prospective Investigation into Cancer-Norfolk (EPIC-Norfolk) with 23 658 completing 7-DFDs at enrolment. The cohort was monitored for 14 years for new symptomatic gallstones, with diagnoses confirmed by review of the clinical notes. The 7-DFDs recorded one week's diet including food types, frequency of consumption, quantities and cooking methods. A representative sample of 3 970 and those with gallstone disease had their 7-DFDs coded by nutritionists using a computer program containing nutrient information on 11 000 food and 55 000 portion sizes. A cohort analysis used Cox regression to estimate sex specific hazard ratios (HR) for developing gallstones comparing fifths of dietary cholesterol
Su1277 Caffeinated Coffee is Associated With a Reduction of Symptomatic Gallstones in Men. Data From a UK Prospective Cohort Study (EPIC-Norfolk) Using 7Day Food Diaries Paul R. Banim, Robert Luben, Stephen J. Sharp, Nick Wareham, Kay-Tee Khaw, Andrew Hart Introduction: Caffeine and coffee may influence gallstone formation by stimulating gallbladder motility and reducing cholesterol saturation of the bile, although not all epidemiological studies have confirmed a protective effect of coffee. The aim of this study was to investigate the effect of caffeinated and decaffeinated coffee and caffeinated tea consumption in a prospective cohort study, for the first time using seven-day food diaries (7-DFDs) which are the most accurate feasible method of estimating dietary intake in large scale epidemiological studies. Methods: 25 639 participants (56% women), aged 40-74 yrs were
S-447
AGA Abstracts
AGA Abstracts
that SIBO was not present in these patients. Conclusion: The duration of low fiber diet to get low hydrogen concentration in the fasting breath of IBS patients may be increased from 24 to 72-hours in north Indian patients to avoid false positive results of SIBO.
Su1274 Dietary Deficiencies of Iron and Niacin in the Aetiology of Symptomatic Gallstones - Data From a UK Prospective Cohort Study (EPIC-Norfolk) Using 7-Day Food Diaries Paul R. Banim, Robert Luben, Kay-Tee Khaw, Stephen J. Sharp, Nick Wareham, Andrew Hart Introduction: Low iron intake reduces nitric oxide synthase (NOS) activity, which impairs gallbladder motility and bile flow. Low iron intake decreases activity of cholesterol 7-αhydroxlase, an enzyme which converts cholesterol to bile acids. Niacin increases plasma high density lipoprotein and lowers plasma triglycerides, both of which are associated with a lower incidence of gallstone disease. This study investigated dietary iron and niacin intake and the risk of developing symptomatic gallstones, for the first time using seven-day food diaries (7-DFDs), the most accurate feasible method of estimating food intake in large epidemiological studies. Methods: 25 639 participants (56% women), aged 40-74 yrs were recruited into the European Prospective Investigation into Cancer-Norfolk (EPIC-Norfolk) with 23 658 completing 7-DFDs at enrolment. The cohort was monitored for 14 years for new symptomatic gallstones, with diagnoses confirmed by review of the clinical notes. The 7-DFDs recorded one week's diet including food types, frequency of consumption, quantities and cooking methods. A representative sample of 3 970 and those with gallstone disease had their 7-DFDs coded by nutritionists using a computer program containing nutrient information on 11 000 food and 55 000 portion sizes. A cohort analysis used Cox regression to estimate sex specific hazard ratios (HR) for developing gallstones comparing fifths of dietary iron and niacin acid intake adjusted for age, body mass index, energy, alcohol and physical activity in men, and also parity and hormone replacement therapy use in women. Results: 177 women (mean age of diagnosis 66.5yrs SD=9.5yrs) and 90 men (64.2yrs SD= 9.2yrs) developed symptomatic gallstones. In women, increased dietary iron intake was associated with a decreased risk of symptomatic gallstones (highest vs lowest fifth, HR=0.36 95% CI=0.20-0.66; per fifth increase, HR=0.82 95% CI=0.72-0.94 p=0.003), although no effects were seen in men (per fifth increase, HR=0.97 95% CI=0.81-1.17). Increased dietary niacin intake was also associated with a decreased risk of disease in women (highest vs lowest fifth, HR=0.50 95% CI=0.30-0.83; per fifth increase, HR=0.86 95% CI=0.76-0.97 p=0.011), but no effects were found in men (per fifth increase, HR=0.96 95% CI=0.811.14). Conclusion: In women, gallstone disease may be prevented by increasing dietary iron and niacin intake, for which there are plausible biological mechanisms. No effects were found in men, although this could be due to a lack of power as only half the number of cases diagnosed and also that men are less likely to be iron deficient. These nutrients should be measured in future studies to confirm the association. Risk of developing symptomatic gallstones by fifths of dietary intake of iron and niacin in women and men.
Decreased dietary cholesterol and increased dietary transfatty acids were associated with an increased risk of developing symptomatic gallstones. HR = Hazard ratio CI = confidence interval Analysis was adjusted for age, body mass index, energy, alcohol and physical acitivity in men with the addition of hormone replacement therapy and parity in women Su1276 Genetic Variation in the Human Interleukin 4 (Il4) Gene is Associated With Gallstone Susceptibility Anke Tönjes, Teresa Strauch, Claudia Ruffert, Joachim Mossner, Michael Stumvoll, Peter Kovacs, Henning Wittenburg Introduction: The individual risk to develop gallstones is determined by risk alleles of gallstone-susceptibility (LITH) genes and their interactions with environmental factors such as rapid weight loss, diet, and specific medications. Quantitative trait locus mapping in the inbred mouse model of cholesterol cholelithiasis identified a Lith locus on mouse chromosome 11, which co-localizes with the Il4 gene. In addition, ablation of Il4 promoted cholesterol gallstone formation in the mouse model of cholelithiasis rendering IL4 an interesting LITH candidate gene based on the presumed concordance of murine and human LITH genes. Methods: To systematically explore the IL4 gene as a LITH gene in humans, we performed a genetic association study in gallstone carriers (N = 184) and control subjects without evidence for gallstones (N = 833) from a self-contained population of Sorbs from Saxony. Based on the HapMap database, three haplotype-tagging single nucleotide polymorphisms (SNPs) (rs2243290, rs2227284 and rs2243263) capturing the genetic variation of IL4 (r2 cutoff 0.8; minor allele frequency > 0.05) were genotyped in cases and controls employing the TaqMan method. Data were analyzed in the additive model using logistic regression including age, sex and body mass index as covariates. The local ethics committee approved the study and all participants gave written informed consent. Results: Two of the three SNPs were associated with cholelithiasis, rs2243290 (P = 0.06) and rs2227284 (P = 0.02). In addition, when only cases with a previous history of a cholecystectomy were considered, both SNPs were significantly associated with symptomatic gallstone disease (rs2243290 (P = 0.009); rs2227284 (P = 0.002)). For both SNPs, an increase in gallstone susceptibility was associated with the variant minor allele. Conclusion: Our results indicate an increased gallstone risk from frequent variants of IL4. Anti-inflammatory mechanisms might explain a protective effect of IL4 on cholelithiasis by up-regulation of PPARγ and a reduction of leukotriene production by inhibition of the arachodinate-5-lipoxygenase. In turn, this might lead to a diminished production of mucin glycoproteins. Accordingly, our findings suggest that IL4 could be a target for prevention and non-surgical management of cholelithiasis in genetically predisposed patients.
Increased dietary iron and niacin intake is associated with a decreased risk of symptomatic gallstones in women. HR = Hazard Ratio CI = Confidence Interval Analysis was adjusted for age, body mass index, energy intake, alcohol intake and physical activity in men with the addition of hormone replacement therapy and parity in women. Su1275 The Role of Dietary Cholesterol and Transfatty Acids in the Aetiology of Gallstones. A UK Prospective Cohort Study (EPIC-Norfolk) Using 7-Day Food Diaries Paul R. Banim, Robert Luben, Stephen J. Sharp, Nick Wareham, Kay-Tee Khaw, Andrew Hart Introduction: Dietary cholesterol may prevent gallstone formation by up-regulating the enzyme cholesterol 7-α hydroxlase (Cyp7a1), which converts cholesterol to primary bile acids and prevents biliary cholesterol supersaturation, a prerequisite for cholesterol stone formation. Transfatty acids promote hyperinsulinaemia which inhibits Cyp7A1 and could promote gallstone disease. This study investigated dietary cholesterol and transfatty acid intake on the risk of developing symptomatic gallstones,for the first time using seven-day food diaries (7-DFDs), the most accurate feasible method of estimating food intake in large studies. Methods: 25 639 participants (56% women), aged 40-74 yrs were recruited into the European Prospective Investigation into Cancer-Norfolk (EPIC-Norfolk) with 23 658 completing 7-DFDs at enrolment. The cohort was monitored for 14 years for new symptomatic gallstones, with diagnoses confirmed by review of the clinical notes. The 7-DFDs recorded one week's diet including food types, frequency of consumption, quantities and cooking methods. A representative sample of 3 970 and those with gallstone disease had their 7-DFDs coded by nutritionists using a computer program containing nutrient information on 11 000 food and 55 000 portion sizes. A cohort analysis used Cox regression to estimate sex specific hazard ratios (HR) for developing gallstones comparing fifths of dietary cholesterol
Su1277 Caffeinated Coffee is Associated With a Reduction of Symptomatic Gallstones in Men. Data From a UK Prospective Cohort Study (EPIC-Norfolk) Using 7Day Food Diaries Paul R. Banim, Robert Luben, Stephen J. Sharp, Nick Wareham, Kay-Tee Khaw, Andrew Hart Introduction: Caffeine and coffee may influence gallstone formation by stimulating gallbladder motility and reducing cholesterol saturation of the bile, although not all epidemiological studies have confirmed a protective effect of coffee. The aim of this study was to investigate the effect of caffeinated and decaffeinated coffee and caffeinated tea consumption in a prospective cohort study, for the first time using seven-day food diaries (7-DFDs) which are the most accurate feasible method of estimating dietary intake in large scale epidemiological studies. Methods: 25 639 participants (56% women), aged 40-74 yrs were
S-447
AGA Abstracts
AGA Abstracts
that SIBO was not present in these patients. Conclusion: The duration of low fiber diet to get low hydrogen concentration in the fasting breath of IBS patients may be increased from 24 to 72-hours in north Indian patients to avoid false positive results of SIBO.