The Chile Biliary Longitudinal Study: A Gallstone Cohort.

Gallbladder cancer (GBC) is a highly fatal cancer that can be cured through cholecystectomy if identified early. The presence of gallstones is the primary risk factor for GBC, but few people with gallstones develop GBC. A key question is what drives the development of GBC among persons with gallstones. We initiated the Chile Biliary Longitudinal Study (Chile BiLS) to address this question. From 2016 to 2019, Chile BiLS enrolled 4,726 women aged 50-74 years with ultrasound-detected gallstones from southern-central Chile, accounting for an estimated 36% of eligible women with gallstones in the study area. The median age was 59 years; 25% of the women were Amerindian (Mapuche), 60% were obese, 25% had diabetes, and 6% had cardiovascular disease. Participants will be followed for gallbladder dysplasia or cancer for 6 years. As of April 30, 2020, over 91% of those eligible completed the year 2 follow-up visit. Data being collected include epidemiologic and sociodemographic information, anthropometric measurements, blood pressure, and tooth counts. Biosamples being taken include baseline plasma, buffy coat, red blood cells, serum, blood clot from serum, and PAXgene whole blood (PreAnalytiX GmbH, Hombrechtikon, Switzerland). Complete gallbladder sampling is conducted for most participants undergoing cholecystectomy. The Chile BiLS cohort study will increase our understanding of GBC etiology and could identify potential risk stratification and early detection strategies in high-risk areas.

Variants in ABCG8 and TRAF3 genes confer risk for gallstone disease in admixed Latinos with Mapuche Native American ancestry.

Latin Americans and Chilean Amerindians have the highest prevalence of gallstone disease (GSD) and gallbladder cancer (GBC) in the world. A handful of loci have been associated with GSD in populations of predominantly European ancestry, however, they only explain a small portion of the genetic component of the disease. Here, we performed a genome-wide association study (GWAS) for GSD in 1,095 admixed Chilean Latinos with Mapuche Native American ancestry. Disease status was assessed by cholecystectomy or abdominal ultrasonography. Top-10 candidate variants surpassing the suggestive cutoff of P < 1 × 10-5 in the discovery cohort were genotyped in an independent replication sample composed of 1,643 individuals. Variants with positive replication were further examined in two European GSD populations and a Chilean GBC cohort. We consistently replicated the association of ABCG8 gene with GSD (rs11887534, P = 3.24 × 10-8, OR = 1.74) and identified TRAF3 (rs12882491, P = 1.11 × 10-7, OR = 1.40) as a novel candidate gene for the disease in admixed Chilean Latinos. ABCG8 and TRAF3 variants also conferred risk to GBC. Gene expression analyses indicated that TRAF3 was significantly decreased in gallbladder (P = 0.015) and duodenal mucosa (P = 0.001) of GSD individuals compared to healthy controls, where according to GTEx data in the small intestine, the presence of the risk allele contributes to the observed effect. We conclude that ABCG8 and TRAF3 genes are associated with GSD and GBC in admixed Latinos and that decreased TRAF3 levels could enhance gallbladder inflammation as is observed in GSD and GSD-associated GBC.

Clinical and ABCB11 profiles in Korean infants with progressive familial intrahepatic cholestasis.

AIM: To investigate clinical profiles and mutations of ABCB11 in Koreans with progressive familial intrahepatic cholestasis 2 and review the differences between Koreans and others. METHODS: Of 47 patients with neonatal cholestasis, five infants had chronic intrahepatic cholestasis with normal γ-glutamyl transpeptidase. Direct sequencing analyses of ABCB11, including exons and introns, were performed from peripheral blood. RESULTS: Living donor-liver transplantation was performed in four patients because of rapidly progressive hepatic failure and hepatocellular carcinoma. Three missense mutations were found in two patients: compound heterozygous 677C>T (S226L)/3007G>A (G1003R) and heterozygous 2296G>A (G766R). The mutations were located near and in the transmembranous space. CONCLUSION: Alterations in the transmembrane of the bile salt export pump in the Korean infants were different from those previously reported in Chinese, Japanease, Taiwanese, and European patients.

Variants and haplotypes in Flap endonuclease 1 and risk of gallbladder cancer and gallstones: a population-based study in China.

The role of FEN1 genetic variants on gallstone and gallbladder cancer susceptibility is unknown. FEN1 SNPs were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method in blood samples from 341 gallbladder cancer patients and 339 healthy controls. The distribution of FEN1-69G > A genotypes among controls (AA, 20.6%; GA, 47.2% and GG 32.2%) was significantly different from that among gallbladder cancer cases (AA, 11.1%; GA, 48.1% and GG, 40.8%), significantly increased association with gallbladder cancer was observed for subjects with both the FEN1-69G > A GA (OR = 1.73, 95% CI = 1.01-2.63) and the FEN1-69G > A GG (OR = 2.29, 95% CI = 1.31-3.9). The distribution of FEN1 -4150T genotypes among controls (TT, 21.8%;GT, 49.3% and GG 28.9%) was significantly different from that among gallbladder cancer cases (TT, 12.9%; GT, 48.4% and GG 38.7%), significantly increased association with gallbladder cancer was observed for subjects with both the FEN1-4150T GT(OR = 1.93, 95% CI = 1.04-2.91) and the FEN1-4150T GG(OR = 2.56, 95% CI = 1.37-5.39). A significant trend towards increased association with gallbladder cancer was observed with potentially higher-risk FEN1-69G > A genotypes (P < 0.001, χ2 trend test) and FEN14150G > T (P < 0.001, χ2 trend test) in gallstone presence but not in gallstone absence (P = 0.81, P = 0.89, respectively). In conclusion, this study revealed firstly that FEN1 polymorphisms and haplotypes are associated with gallbladder cancer risk.

Cholecystectomy is independently associated with nonalcoholic fatty liver disease in an Asian population.

AIM: To investigate the relationship between gallstone disease and nonalcoholic fatty liver disease (NAFLD) in a large Asian population. METHODS: A cross-sectional study including 17612 subjects recruited from general health check-ups at the Seoul National University Hospital, Healthcare System Gangnam Center between January 2010 and December 2010 was conducted. NAFLD and gallstone disease were diagnosed based on typical ultrasonographic findings. Subjects who were positive for hepatitis B or C, or who had a history of heavy alcohol consumption (> 30 g/d for men and > 20 g/d for women) or another type of hepatitis were excluded. Gallstone disease was defined as either the presence of gallstones or previous cholecystectomy, and these two entities (gallstones and cholecystectomy) were analyzed separately. Clinical parameters including body mass index, waist circumference, hypertension, diabetes, smoking status, and regular physical activity were reviewed. Laboratory parameters, including serum levels of gamma-glutamyl transpeptidase, alanine aminotransferase, aspartate aminotransferase, fasting glucose, fasting insulin, total cholesterol, triglycerides, and high-density lipoprotein, were also reviewed. RESULTS: The mean age of the subjects was 48.5 ± 11.3 years, and 49.3% were male. Approximately 30.3% and 6.1% of the subjects had NAFLD and gallstone disease, respectively. The prevalence of gallstone disease (8.3% vs 5.1%, P < 0.001), including both the presence of gallstones (5.5% vs 3.4%, P < 0.001) and a history of cholecystectomy (2.8% vs 1.7%, P < 0.001), was significantly increased in the NAFLD group. In the same manner, the prevalence of NAFLD increased with the presence of gallstone disease (41.3% vs 29.6%, P < 0.001). Multivariate regression analysis showed that cholecystectomy was associated with NAFLD (OR = 1.35, 95%CI: 1.03-1.77, P = 0.028). However, gallstones were not associated with NAFLD (OR = 1.15, 95%CI: 0.95-1.39, P = 0.153). The independent association between cholecystectomy and NAFLD was still significant after additional adjustment for insulin resistance (OR = 1.45, 95%CI: 1.01-2.08, P = 0.045). CONCLUSION: This study shows that cholecystectomy, but not gallstones, is independently associated with NAFLD after adjustment for metabolic risk factors. These data suggest that cholecystectomy may be an independent risk factor for NAFLD.

Roles of ApoB-100 gene polymorphisms and the risks of gallstones and gallbladder cancer: a meta-analysis.

BACKGROUND: Gallstones (GS) is the major manifestation of gallbladder disease, and is the most common risk factor for gallbladder cancer (GBC). Previous studies investigating the association between ApoB-100 gene polymorphisms and the risks of GS and GBC have yielded conflicting results. Therefore, we performed a meta-analysis to clarify the effects of ApoB-100 gene polymorphisms on the risks of GS and GBC. METHODS: A computerized literature search was conducted to identify the relevant studies from PubMed and Embase. Fixed or random effects model was selected based on heterogeneity test. Publication bias was estimated using Begg's funnel plots and Egger's regression test. RESULTS: A total of 10, 3, and 3 studies were included in the analyses of the association between ApoB-100 XbaI, EcoRI, or insertion/deletion (ID) polymorphisms and the GS risks, respectively, while 3 studies were included in the analysis for the association between XbaI polymorphism and GBC risk. The combined results showed a significant association in Chinese (X+ vs. X-, OR = 2.37, 95%CI 1.52-3.70; X+X+/X+X- vs. X+X+, OR = 2.47, 95%CI 1.55-3.92), but not in Indians or Caucasians. Null association was observed between EcoRI or ID polymorphisms and GS risks. With regard to the association between XbaI polymorphism and GBC risk, a significant association was detected when GBC patients were compared with healthy persons and when GBC patients were compared with GS patients. A significant association was still detected when GBC patients (with GS) were compared with the GS patients (X+X+ vs. X-X-, OR = 0.33, 95%CI 0.12-0.90). CONCLUSION: The results of this meta-analysis suggest that the ApoB-100 X+ allele might be associated with increased risk of GS in Chinese but not in other populations, while the ApoB-100 X+X+ genotype might be associated with reduced risk of GBC. Further studies with larger sample sizes are needed to confirm these results.

The prevalence and risk factors of gallstones in Korean patients with liver cirrhosis.

BACKGROUND/AIMS: The aims of this study were to evaluate the frequency of gallstones and the related risk factors in patients with liver cirrhosis. METHODOLOGY: Patients (n=1,333) with liver cirrhosis who were diagnosed at Yeungnam University Hospital between January 2006 and December 2008 were analyzed retrospectively. Healthy people (n=16,922) who underwent an examination at the health promotion center were enrolled as a control group. We analyzed the clinical and laboratory findings between the cirrhotic patients with and without gallstones. RESULTS: Liver cirrhosis was an independent risk factor for gallstone formation (OR: 2.017; p=0.00). Diabetes and hypertriglyceridemia increased the risk for gallstones by 2.2-fold and 1.9-fold in cirrhotic patents, respectively. The severity of the liver cirrhosis according to the Child-Pugh class carried a significantly greater risk of gallstone formation. Multiple logistic regression analysis showed that diabetes, hypertriglyceridemia, and Child-Pugh class C were significantly related to the risk of gallstone formation in patients with liver cirrhosis. CONCLUSIONS: The prevalence of gallstones is significantly higher in patients with liver cirrhosis, and the related risk factors are diabetes, hypertriglyceridemia and severity of liver cirrhosis.

Genetics of biliary lithiasis from an ethnic perspective.

Gallstone disease represents one of the most common gastroenterological disorders worldwide. Gallstones affect over 15% of adults in Europe and 25-30% of Hispanic populations in Central and South America. The heritability of gallstones varies considerably according to ethnicity, with Native Americans and Hispanics with Amerindian admixture being the most susceptible populations. Genetic factors have been shown to account for 25-30% of total gallstone risk in Europe, however, in Hispanic populations, this risk percentage may increase to 45-65%. Recent genome-wide association and candidate gene studies have identified common polymorphisms in enterohepatic transporters (ABCG5/8, SLC10A2) and the Gilbert syndrome UGT1A1 variant as genetic determinants of gallstone formation. Together, these polymorphisms cover a significant proportion of the previously predicted genetic background of gallstones in European populations. New lithogenic genes need to be discovered in future studies in high-risk populations. In this review, we address the latest developments in the genetic analysis of gallstones and discuss the ethnic background of this condition in European, Central and South American and Asian populations.

Gallstones in New Zealand: composition, risk factors and ethnic differences.

BACKGROUND: Gallstone disease is a worldwide problem causing morbidity, mortality and a drain on health-care resources. This prospective study aimed to investigate the spectrum of gallstone types in New Zealand and relate these to known risk factors. METHODS: Gallstone samples were collected from 107 patients undergoing surgery for gallstone disease at Auckland City Hospital between June 2009 and June 2010. Detailed chemical analyses were performed using Fourier Transform Raman spectroscopy. The relationship between gallstone type and age, gender, ethnicity, obesity and positive family history were analysed. RESULTS: Median age was 51 years (range 19-88), 75 (70%) were female, one third were obese (body mass index ≥ 30) and 41% had a positive family history. Major ethnic groups were European (51%), Asian (23%) and Maori/Pacific (18%). Gallstone types included pure or mixed cholesterol stones (74%), black pigment stones (20%) and brown pigment stones (5%). Asians had a higher proportion of black pigment stones and NZ Europeans had more cholesterol and mixed cholesterol stones (odds ratio 3.6 (95% CI 1.1 to 11.5)). The frequency of cholesterol/mixed cholesterol stones was not significantly different between NZ Europeans and Maori/Pacific groups (P = 0.7). Black pigment stones were more common in older patients (mean 68.0 years compared with 47.6 for cholesterol/mixed cholesterol stones) (P = 0.0001). There was no significant relationship between stone type and family history (P = 0.16) or gender (P = 0.17). CONCLUSION: This novel prospective study highlights risk factors and ethnic differences in gallstone composition in New Zealand. These may be important when considering gallstone prevention strategies.

Single nucleotide polymorphism rs3732860 in the 3'-untranslated region of CYP8B1 gene is associated with gallstone disease in Han Chinese.

BACKGROUND AND AIMS: Gallstone disease (GD) is a common disease of multigenetic origin; however, the major susceptibility loci for GD in human populations remain unidentified. This study aimed to identify the genetic factors contributing to gallstone development in Chinese. METHODS: A genome-wide scan was conducted in 12 Han Chinese GD families to identify linkage loci. The linkage region showing the highest logarithm of odds score encompasses the sterol 12α-hydroxylase gene (CYP8B1). Replication analysis with an independent sample of 192 GD patients and 192 unrelated, matched controls was carried out to verify the associations between CYP8B1 polymorphisms and GD. RESULTS: Three loci (D3S1266, D4S406, and D9S1682) showed suggestive or nominal evidence of linkage in all 12 GD families. The logarithm of odds score of D3S1266 reached 2.71 in the families with late-onset patients. The single nucleotide polymorphism rs3732860 in the 3'-untranslated region of CYP8B1 showed significant association to GD (P = 0.022), and carriers of the A allele had lower risk of GD (odds ratio = 1.46, 95% confidence interval: 1.055-2.034) compared with carriers of the G allele. CONCLUSIONS: The single nucleotide polymorphism rs3732860 in the 3'-untranslated region of the CYP8B1 gene is associated with risk of GD in Chinese Han and appears to be responsible for the observed linkage with D3S1266.

Phytosterol and cholesterol precursor levels indicate increased cholesterol excretion and biosynthesis in gallstone disease.

UNLABELLED: In hepatocytes and enterocytes sterol uptake and secretion is mediated by Niemann-Pick C1-like 1 (NPC1L1) and ATP-binding cassette (ABC)G5/8 proteins, respectively. Whereas serum levels of phytosterols represent surrogate markers for intestinal cholesterol absorption, cholesterol precursors reflect cholesterol biosynthesis. Here we compare serum and biliary sterol levels in ethnically different populations of patients with gallstone disease (GSD) and stone-free controls to identify differences in cholesterol transport and synthesis between these groups. In this case-control study four cohorts were analyzed: 112 German patients with GSD and 152 controls; two distinct Chilean ethnic groups: Hispanics (100 GSD, 100 controls), and Amerindians (20 GSD, 20 controls); additionally an 8-year follow-up of 70 Hispanics was performed. Serum sterols were measured by gas chromatography / mass spectrometry. Gallbladder bile sterol levels were analyzed in cholesterol GSD and controls. Common ABCG5/8 variants were genotyped. Comparison of serum sterols showed lower levels of phytosterols and higher levels of cholesterol precursors in GSD patients than in controls. The ratios of phytosterols to cholesterol precursors were lower in GSD patients, whereas biliary phytosterol and cholesterol concentrations were elevated as compared with controls. In the follow-up study, serum phytosterol levels were significantly lower even before GSD was detectable by ultrasound. An ethnic gradient in the ratios of phytosterols to cholesterol precursors was apparent (Germans > Hispanics > Amerindians). ABCG5/8 variants did not fully explain the sterol metabolic trait of GSD in any of the cohorts. CONCLUSION: Individuals predisposed to GSD display increased biliary output of cholesterol in the setting of relatively low intestinal cholesterol absorption, indicating enhanced whole-body sterol clearance. This metabolic trait precedes gallstone formation and is a feature of ethnic groups at higher risk of cholesterol GSD.

Clinical characteristics and risk factors for symptomatic pediatric gallbladder disease.

OBJECTIVE: Our center previously reported its experience with pediatric gallbladder disease and cholecystectomies from 1980 to 1996. We aimed to determine the current clinical characteristics and risk factors for symptomatic pediatric gallbladder disease and cholecystectomies and compare these findings with our historical series. STUDY DESIGN: Retrospective, cross-sectional study of children, 0 to 18 years of age, who underwent a cholecystectomy from January 2005 to October 2008. RESULTS: We evaluated 404 patients: 73% girls; 39% Hispanic and 35% white. The mean age was 13.10 ± 0.91 years. The primary indications for surgery in patients 3 years or older were symptomatic cholelithiasis (53%), obstructive disease (28%), and biliary dyskinesia (16%). The median BMI percentile was 89%; 39% were classified as obese. Of the patients with nonhemolytic gallstone disease, 35% were obese and 18% were severely obese; BMI percentile was 99% or higher. Gallstone disease was associated with hemolytic disease in 23% (73/324) of patients and with obesity in 39% (126/324). Logistic regression demonstrated older age (P = .019) and Hispanic ethnicity (P < .0001) as independent risk factors for nonhemolytic gallstone disease. Compared with our historical series, children undergoing cholecystectomy are more likely to be Hispanic (P = .003) and severely obese (P < .0279). CONCLUSION: Obesity and Hispanic ethnicity are strongly correlated with symptomatic pediatric gallbladder disease. In comparison with our historical series, hemolytic disease is no longer the predominant risk factor for symptomatic gallstone disease in children.

Ethnicity and insurance status affect health disparities in patients with gallstone disease.

BACKGROUND: Complex gallstone disease is associated with greater risk of morbidity, associated with operative complications and longer hospital stays. The purpose of this study is to evaluate whether ethnicity or insurance status is associated with differences in presentation and outcomes in gallstone disease. MATERIALS AND METHODS: A retrospective analysis was performed for all patients who underwent cholecystectomy between August 1, 2007 and May 31, 2010 at the only teaching hospital in the region. Analysis of Variance, Chi square (χ(2)) and logistical regression analyses were used to evaluate the impact of ethnicity and insurance status on the complexity of gallstone disease and surgical outcomes. RESULTS: A total of 562 patients had a cholecystectomy during the study period, of whom 255 (45.4%) were Latino. Latino patients were significantly younger than any other ethnic group (P < 0.001) and had a significantly higher rate of being uninsured (40%, P = 0.03). Latino patients were significantly more likely to require ERCP (38.6% versus 28.8% for non-Latino, P = 0.01). Latino patients had a significantly higher white blood cell count (P = 0.017). There were no significant differences in liver function tests, bilirubin levels, albumin levels, hospital lengths of stay, operation types, pathology types, or complication rates between ethnic groups. Uninsured patients were significantly younger (P = 0.003) and were more likely to require an ERCP (39.5% versus 26.8% for privately insured and 31.9% for publicly insured, P = 0.04). Patients with no insurance were significantly more likely to have a higher white blood cell count (P = 0.039) and aspartate aminotransferase (AST) level (P = 0.04). Patients with public insurance and no insurance had a significantly longer median length of hospital stay (4.0 d versus 3.0 d for privately insured, P = 0.045). There were no significant differences in operation types, complication rates, or pathologic diagnosis based on insurance status. CONCLUSIONS: In our population, ethnicity and insurance status do play a role in the presentation and care of patients with gallstone disease. Latino and uninsured patients present with a higher complexity of disease and require interventions more frequently.

Insulin resistance as a risk factor for gallbladder stone formation in Korean postmenopausal women.

BACKGROUND/AIMS: The objective of this study was to determine whether insulin resistance is associated with gallbladder stone formation in Korean women based on menopausal status. METHODS: The study included 4,125 consecutive Korean subjects (30-79 years of age). Subjects who had a medical history of diabetes, hypertension, dyslipidemia, other cardiovascular disorders, or hormone replacement therapy were excluded. The women were subdivided into two groups according to their menopausal status. RESULTS: Analysis of premenopausal women showed no significant differences in the homeostasis model of assessment-insulin resistance (HOMA-IR) index between the two groups in terms of gallstone disease. The associations between the occurrence of gallbladder stones and age, obesity, abdominal obesity, hyperinsulinemia, and high HOMA-IR index were statistically significant in the analysis with postmenopausal women. In a multiple logistic regression analysis, low high density lipoprotein-cholesterol was an independent predictor of gallbladder stone formation in premenopausal women. However, the multiple logistic regression analysis also showed that age and HOMA-IR were significantly associated with gallbladder stone formation in postmenopausal women. In an additional analysis stratified by obesity, insulin resistance was a significant risk factor for gallbladder stone formation only in the abdominally obese premenopausal group. CONCLUSIONS: Insulin resistance may be associated with gallbladder stone formation in Korean postmenopausal women with abdominal obesity.

Sterol transporter adenosine triphosphate-binding cassette transporter G8, gallstones, and biliary cancer in 62,000 individuals from the general population.

UNLABELLED: Gallstone disease, a risk factor for biliary cancer, has a strong heritable component, but the underlying genes are largely unknown. To test the hypothesis that ABCG8 (adenosine triphosphate-binding cassette transporter G8) Asp19His (D19H) genotype predicted risk of gallstones and biliary cancer in the general population, we studied 62,279 white individuals from The Copenhagen City Heart Study and The Copenhagen General Population Study, randomly selected to reflect the adult Danish population aged 20 to 80+ years. Endpoints were recorded from January 1976 through May 2009. During a mean follow-up of, respectively, 31 and 4.4 years, 3124 participants developed symptomatic gallstone disease and 30 developed biliary cancer. The multifactorially adjusted hazard ratio for symptomatic gallstone disease was 1.9 (95% confidence interval, 1.7-2.1) in DH heterozygotes (prevalence, 12%), and 3.3 (2.3-4.6) in HH homozygotes (0.4%) versus noncarriers (P for trend <0.001). Mean age at onset of symptomatic gallstone disease was 56 years for noncarriers, 54 for DH heterozygotes, and 52 for HH homozygotes (P for trend <0.001). The fraction of all gallstones attributed to D19H was 11%. The multifactorially adjusted hazard ratio for biliary cancer was 4.0 (1.9-8.4) in DH heterozygotes and HH homozygotes combined versus noncarriers (P < 0.001). The fraction of all biliary cancers attributed to the D19H genotype was 27%. Finally, D19H genotype associated with stepwise increases in plasma levels of alanine aminotransferase and gamma glutamyltransferase of up to 14% and 25% in HH homozygotes, and with corresponding stepwise reductions in plasma levels of total and low-density lipoprotein cholesterol of up to 5% versus noncarriers (all comparisons, P for trend <0.001). CONCLUSION: In this general population cohort, ABCG8 D19H genotype was an important predictor of both symptomatic gallstone disease and biliary cancer.

Insulin Resistance as a Risk Factor for Gallbladder Stone Formation in Korean Postmenopausal Women

BACKGROUND/AIMS: The objective of this study was to determine whether insulin resistance is associated with gallbladder stone formation in Korean women based on menopausal status. METHODS: The study included 4,125 consecutive Korean subjects (30-79 years of age). Subjects who had a medical history of diabetes, hypertension, dyslipidemia, other cardiovascular disorders, or hormone replacement therapy were excluded. The women were subdivided into two groups according to their menopausal status. RESULTS: Analysis of premenopausal women showed no significant differences in the homeostasis model of assessment-insulin resistance (HOMA-IR) index between the two groups in terms of gallstone disease. The associations between the occurrence of gallbladder stones and age, obesity, abdominal obesity, hyperinsulinemia, and high HOMA-IR index were statistically significant in the analysis with postmenopausal women. In a multiple logistic regression analysis, low high density lipoprotein-cholesterol was an independent predictor of gallbladder stone formation in premenopausal women. However, the multiple logistic regression analysis also showed that age and HOMA-IR were significantly associated with gallbladder stone formation in postmenopausal women. In an additional analysis stratified by obesity, insulin resistance was a significant risk factor for gallbladder stone formation only in the abdominally obese premenopausal group. CONCLUSIONS: Insulin resistance may be associated with gallbladder stone formation in Korean postmenopausal women with abdominal obesity.

Correlates of kidney stone disease differ by race in a multi-ethnic middle-aged population: the ARIC study.

OBJECTIVE: To identify correlates of kidney stone disease in white and African American men and women in a population-based longitudinal study starting in four US communities, and to assess differences in correlates across racial groups. METHODS: Between 1993 and 1995, 12,161 middle-aged participants of the ARIC Study provided information on history of kidney stone disease. Information on incident kidney stone-related hospitalizations was obtained from ICD codes on hospital discharge records. RESULTS: Kidney stone disease was reported by 12.0% of men and 4.8% of women. After multivariable adjustment, prevalent kidney stone disease was significantly (p<0.05) associated with male gender (PR=2.50), increased serum triglycerides (PR=1.07 per SD increase), diabetes (PR=1.27), gallstone disease (PR=1.54), white race (PR=1.67), and region of residence. Male gender (HR=1.70), diabetes (HR=1.98), and hypertension (HR=1.69) were significantly associated (p<0.05) with incident kidney stone-related hospitalizations (n=94). Race-stratified analyses showed stronger associations of prevalent kidney stone disease with increased triglycerides, older age, and gallstone disease in African Americans compared to whites, whereas male gender showed stronger association in whites (all p-interaction<0.05). CONCLUSION: We identified novel correlates of kidney stone disease (triglycerides, gallstone disease) and risk factor interactions by race (age, male gender, triglycerides, gallstone disease).

Genetic variants involved in gallstone formation and capsaicin metabolism, and the risk of gallbladder cancer in Chilean women.

AIM: To determine the effects of genetic variants associated with gallstone formation and capsaicin (a pungent component of chili pepper) metabolism on the risk of gallbladder cancer (GBC). METHODS: A total of 57 patients with GBC, 119 patients with gallstones, and 70 controls were enrolled in this study. DNA was extracted from their blood or paraffin block sample using standard commercial kits. The statuses of the genetic variants were assayed using Taqman SNP Genotyping Assays or Custom Taqman SNP Genotyping Assays. RESULTS: The non-ancestral T/T genotype of apolipoprotein B rs693 polymorphism was associated with a decreased risk of GBC (OR: 0.14, 95% CI: 0.03-0.63). The T/T genotype of cholesteryl ester transfer protein (CETP) rs708272 polymorphism was associated with an increased risk of GBC (OR: 5.04, 95% CI: 1.43-17.8). CONCLUSION: Genetic variants involved in gallstone formation such as the apolipoprotein B rs693 and CETP rs708272 polymorphisms may be related to the risk of developing GBC in Chilean women.