Risk Of Gallstone Disease Research Articles

Risk of Gallstone Disease in Primary Hyperparathyroidism: A Systematic Review and Meta-analysis

ObjectiveApart from renal stones, primary hyperparathyroidism (PHPT) has been linked to the occurrence of gallstone disease (GSD). Nevertheless, the association is not consistent across all studies. The present systematic review and meta-analysis aims to collate the hitherto available evidence and provide a pooled estimate of the association between GSD and PHPT. MethodsPubMed/MEDLINE, Embase, and Web of Science databases were systematically searched from inception till May 10, 2023 for observational studies reporting the prevalence of GSD (in terms of absolute numbers) in patients with PHPT. The pooled prevalence of GSD and odds ratio with 95% CI of the occurrence of GSD in patients with PHPT as compared to age- and sex-matched controls were calculated. Subgroup analysis was performed based on patient ethnicity (Indian/Caucasian). Statistical analysis was carried out using R version 4.2.2. Random-effects model with Hartung-Knapp adjustment was used for analyses. ResultsA total of 7 observational studies were included, pooling data from 15 949 patients with PHPT. The pooled prevalence of GSD in patients with PHPT was 16% (95% CI: 7%, 25%, I2 = 99%), being 13% (95% CI: 0%, 66%, I2 = 76%) in Indians, and 17% (95% CI: 4%, 31%, I2 = 99%) in Caucasians. Data consolidated from 3 studies showed that the pooled odds ratio of occurrence of GSD in patients with PHPT compared to controls was 1.77 (95% CI: 1.60, 1.97, P < .001, I2 = 0%). ConclusionsGSD is more prevalent in patients with PHPT than in the general population. Thus, PHPT may be considered an additional risk factor for GSD.

Abstract 14943: Trans-Biobank Mendelian Randomization Analyses Identify Distinct and Opposing Pathways in the Association of Lower Plasma Low-Density Lipoprotein-Cholesterol With Risk of Gallstone Disease

Background: Higher plasma LDL-cholesterol increases coronary artery disease risk, while biliary cholesterol promotes gallstone formation. Trial evidence suggests that lowering plasma LDL-cholesterol with bempedoic acid increases gallstone risk. Hypothesis: Different plasma LDL-cholesterol lowering pathways have distinct effects on biliary cholesterol and thereby gallstone disease risk. Methods: We conducted a Mendelian randomization (MR) study using data from the UK Biobank (30,547 gallstone disease cases/336,742 controls), FinnGen (34,461 cases/301,383 controls) and Biobank Japan (9,305 cases/168,253 controls). We firstly performed drug-target MR analyses substantiated by colocalization to investigate the effects of plasma LDL-cholesterol lowering therapies on gallstone risk. We then performed clustered MR analyses followed by pathway analyses to identify distinct pathways in the association of lower plasma LDL-cholesterol with gallstone risk. Results: Genetic mimics of statins were associated with lower gallstone risk, but genetic mimics of PCSK9 inhibitors, mipomersen and bile acid sequestrants were associated with higher gallstone risk. The association for statins was supported by colocalization (posterior probability 98.7%). Clustered MR analyses consistently identified clusters showing opposing associations of lower plasma LDL-cholesterol with gallstone risk. Among variants predicting lower plasma LDL-cholesterol, those associated with lower gallstone risk were mapped to glycosphingolipid biosynthesis pathway, while those associated with higher gallstone risk were mapped to pathways relating to ATP-binding cassette transporters and plasma lipoprotein assembly, remodelling, and clearance. Conclusions: Genetic evidence suggests that different plasma LDL-cholesterol lowering pathways may have opposing effects on gallstone disease risk. Specifically, statins may reduce gallstone disease risk.

Are children with gallstone disease more overweight? Results of a matched case-control analysis.

Gallstone disease (GD) is increasingly common among children, possibly caused by an unhealthy food environment and the associated unhealthy lifestyle. In this study, we investigate the association between body weight and gallstone risk in a cohort of prospectively recruited children with GD. We analysed 188 children with gallstones (50.0% girls, median age 9.8 years) and 376 children without stones who were age- and gender-matched to cases in a ratio of 2:1. Cases were prospectively recruited at three Polish university centres (Warsaw, Katowice and Bialystok). Gallstones were diagnosed by either abdominal sonography or by a history of cholecystectomy. Matched controls without gallstones were selected from 22,412 children taking part in nationally representative polish health surveys (OLA and OLAF studies) which provided height and weight data for randomly selected pre-school (2.5-6 years) and school aged (7-18 years) children and adolescents. Analysis of the age- and gender-matched cases and controls demonstrated that patients with GD had significantly higher BMI (P = 0.02) and BMI z-score (P < 0.01) than children without stones. Children with gallstones were more frequently overweight (35.6%, P < 0.01) and obese (12.2%, P < 0.01) than controls (18.4% and 6.7%, respectively). Regression analyses showed that BMI, BMI z-score, overweight and obesity were all associated with increased GD risk (all P < 0.05). Overweight and obesity are common in children with cholelithiasis. Given the prevalence obesity in children we should expect an increasing prevalence of gallstones and stone-related complications in youths and in adults.

Dietary inflammatory index and risk of gallstone disease in Iranian women: a case-control study

BackgroundConsidering inflammation as a primary occurrence in gallstone formation, this study aimed to determine the relation between serum biomarkers of inflammation and oxidative stress, and dietary Inflammatory Index (DII) score with the risk of gallstone disease (GD) among Iranian women.Materials and methodsPresent BMI-matched case-control study was performed among 75 women with GD and 75 healthy controls. Biochemical parameters were measured by standard laboratory methods. A validated food frequency questionnaire (FFQ) was used to assess the usual intake of participants. DII score was calculated for all participants. The linear and logistic regression were used to examine the association of DII with serum inflammatory biomarkers and the odds ratio of GD, respectively.ResultsThe mean serum levels of high-sensitivity C-reactive protein (hs-CRP) and Malondialdehyde (MDA) were significantly (P < 0.001) higher in GD patients compared to control subjects. Women in the highest tertile of DII compared to the lowest tertile had lower intake of macronutrients, minerals, vitamins garlic, onion, pepper and fiber. Moreover, the odd of GD was significantly higher in the third tertile of the DII versus the first tertile after adjustment of potential confounders (OR: 17.47; 95% CI: 4.64–65.72). Also, a positive and significant relationship was found between the serum level of inflammatory biomarkers with the risk of GD and the inflammatory score of the diet (P < 0.001).ConclusionOur data indicate that higher DII score, and serum inflammatory and oxidative stress biomarkers are related to higher risk of GD in Iranian women.

Dietary patterns and gallstone risks in Chinese adults: a cross-sectional analysis of China Multi-Ethnic Cohort Study.

Background Little is known about the association between a plant-based diet and the risk of Gallstone disease (GD), especially in developing counties. We tested the hypothesis that the shifting dietary pattern would be related to the risk of GD, and the Mediterranean diet (MED) adjusted for China was still beneficial for the lower risk of GD.Methods Data were extracted from the baseline survey of the China Multi-Ethnic Cohort study. An alternative Mediterranean diet (aMED) score was accessed based on the food frequency questionnaire and three posteriori dietary patterns (the modern dietary pattern, the coarse grain dietary pattern, and the rice dietary pattern) were identified by factor analysis. Multivariable logistic regression models were developed to evaluate the association between dietary patterns and GD risks.Results A total of 89 544 participants were included. The prevalence of GD was 7.5%. Comparing the highest with lowest quintiles, aMED was associated with an increased risk of GD (OR:1.13; 95% CI:1.04-1.24; p trend = 0.003), whereas the rice dietary pattern was inversely related to GD risk (OR: 0.79; 95% CI:0.71-0.87; p trend < 0.001). After the stratified analysis, the rice dietary pattern has a stronger inverse association in the subgroup of female, the older, the urban, the fat, and diabetes-factors associated with higher rates of GD in previous studies.Conclusion Higher adherence to the rice dietary pattern was associated with a lower risk of GD. For the high-risk populations, making some shift to a traditional agricultural diet might help with the primary prevention of GD.

Correlation of serum biochemical characteristics and ABCG8 genetic variant (rs 11887534) with gall stone compositions and risk of gallstone disease in a group of Egyptian patients.

The overexpression of the cholesterol transporter: ATP-binding cassette transporter (ABCG8) due to the effect of ABCG8 genetic variant (rs11887534) leads to the precipitation of cholesterol crystals and gallstone disease (GSD). To evaluate the chemical composition of gallstones and the role of ABCG8 (rs11887534) in the susceptibility to GSD. We enrolled 77 patients with GSD treated with standard laparoscopic or open cholecystectomy and 75 age and sex-matched healthy controls. Chemical analysis of the extracted gallstones was performed. Analysis of the rs11887534 was performed by real-time PCR TaqMan technique for both cases and controls. Pure cholesterol stones were the main type of stones in GSD patients. The CC genotype carriers of rs11887534 were more prone to gallstone formation than other genotypes. The CC genotype carriers were 100 folds at increased risk to develop pure cholesterol stones. The most prevalent type of gallbladder stones is pure cholesterol stone. ABCG8 (rs11887534) could be associated with increased risk for cholesterol gallstones formation, this risk was more pronounced in female patients.

Abdominal obesity mediates the causal relationship between depression and the risk of gallstone disease: retrospective cohort study and Mendelian randomization analyses

ObjectiveOur study aimed to explore the causal effect of depression on the risk of gallstone disease, and the mediation effects of metabolic traits. MethodsA retrospective cohort study on Chinese elderly from the Dongfeng-Tongji cohort (including 18,141 individuals) was conducted to estimate the adverse effect of probable depression on the risk of gallstone disease. Two-sample Mendelian randomization was performed in European and East-Asian ancestries, to verify the causal relationship between major depression and gallstone disease. We further applied two-step Mendelian randomization to explore the mediation effects of metabolic traits. ResultsIn the cohort study, probable depression was associated with an increased risk of gallstone disease within 5 years, with RR (95% CI) of 1.33 (1.12, 1.58) in multivariable regression, and 1.34 (1.11, 1.61) following propensity score weighting. Bidirectional Mendelian randomization in European ancestry revealed a positive causal effect (OR: 1.21; 95% CI: 1.07 to 1.37) of genetically predicted major depression liability on gallstone disease, based on the inverse variance weighted method. Little evidence was presented from other complementary approaches, and the analysis in East-Asian ancestry (IVW estimated OR: 1.03; 95% CI: 0.92 to 1.15). The indirect effect via waist circumference and HDL-C were 1.06 (95% CI: 1.02 to 1.10) and 1.01 (95% CI: 1.00 to 1.01) respectively, which mediated 25.8% and 3.78% of the causal relationship. ConclusionsOur study suggested a higher risk of gallstone disease in the population with probable depression, while the two-sample Mendelian randomization provided weak evidence for the causal relationship, which was moderately mediated by abdominal obesity.

Physical Activity and Gallstone Disease

Аim: to present data of Russian and foreign studies about association between physical activity (PA) and gallstone disease (GSD).Key point. A low PA level is one of the four major risk factors for chronic non-infectiuos diseases. The frequency of low PA in men and women of the Russian Federation (according to the medical examination in 2016) is 19 %. The global prevalence of GSD is up to 20 % among adults. Many systematic reviews and meta-analyses have confirmed an inverse association between GSD and PA in the world, regardless of potential risk factors for GSD, with a clear dose-dependent effect — the relative risk (RR) of GSD was 0.87 (95 % CI 0.83–0.92) per 20 metabolic equivalents (MET) of PA per week. According to our results of an epidemiological survey in the framework of the WHO MONICA program in Novosibirsk (n = 870) among women aged 25–64 with low total PA (less than 800 MET/min/week), as well as with the first class of PA in leisure-time, GSD occurred much more often (class 1 — 33 %, classes 2–4 — 8.7–11.0 %, p &lt; 0.01). PA favorably affects almost all mechanisms of gallstone formation: improves cholesterol metabolism in bile, increases serum HDL cholesterol, bile acid synthesis, stimulates the release of cholecystokinin, reduces mucin hypersecretion, increases the diversity and richness of the intestinal microbiota. Daily PA serves as a preventive measure for GSD: the risk of GSD is reduced by 66 % (95 % CI 0.18–0.86).Conclusion. EASL has recognized PA as a protective agent against gallstone formation.

Apolypoprotein E gene polymorphism, gallstone disease, diabetes 2 type and lipid metabolism disorders

Aim of the study was to explore the impact of apolipoprotein E (APOE) gene polymorphisms (GP) on gallstone disease (GSD) and type 2 diabetes mellitus (DM2) and its role in lipid metabolism. APOE4 allele carriers had the highest levels of plasma and bile cholesterol and the lowest levels of bile acids in bile than other alleles. In GSD a higher frequency of APOE4 carriers (2.6 times compared to control) was found. GSD risk was reduced by 12 % in APOE2 carriers compared to APOE3/3. Our 20-year research confirms the association of APOE GP and GSD. The frequency of ε4/ε4 genotype is higher in people aged 18–35 years with a family history of GSD (5.8 %) compared to population of Novosibirsk (1.8 %, p &lt; 0.05). The bile was more lithogenic in APOE4 carriers with GSD: the bile cholesterol level is 8.0 ± 0.5 versus 6.9 ± 0.6 g/l in ε3/ε3 genotype. APOE4 carriers with a family history of GSD had cholate-cholesterol ratio of 6.4 ± 0.7 versus 12.9 ± 0.2 (p &lt; 0.05) in the absence of APOE4. in women with hypertension, the presence of GSD was associated with a combination of low density cholesterol (LDL-C) &gt; 3.5 mmol/l and the APOE4 carriage. DM2 is a recognized risk factor for GSD. The most common opinion is that the ε4 allele is an independent risk of DM2, some authors consider the allele APOE2. Moreover, DM2 patients with the ε3/ε4 genotype have an increase in total cholesterol, LDL-C and non-high-density lipoprotein cholesterol compared to ε3/ε3. Other studies have not found any associations between APOE GP and GSD or DM2. The inconsistency of the data can be explained by the heterogeneity of the included groups and methods of APOE genotyping, which requires further research.

Associations of long-term exposure to particulate matter with gallstone risks in Chinese adults: A large cross-sectional study

BackgroundEpidemiological evidence regarding the relation of exposure to ambient particulate matter (PM) with gallstone disease (GSD) risk remains lacking. We tested the hypothesis that long-term exposure to PM is related to the development of GSD and that dyslipidemia can mediate the effect of PM-associated GSD formation. MethodsWe extracted related information on the basis of the baseline survey of the China Multi-Ethnic Cohort Study. The exposure levels of PM (PM1, PM2.5, and PM10) were assessed by validated spatiotemporal models. The relation of exposure to ambient PM with GSD risks was analyzed by non-conditional logistic regression models. Additionally, mediation analysis was conducted to assess whether dyslipidemia was related to the relation of PM exposure with GSD risks. ResultsA total of 72,893 participants were included. Increased ambient PM exposure was positively associated with a higher GSD risk, with ORs (and 95% CI) of 1.17 (1.06, 1.28), 1.10 (1.05, 1.15), and 1.07 (1.04, 1.10) for every 10 μg/m3 increment in PM1, PM2.5, and PM10, separately. The association was more remarkable in males, drinkers, and central obesity participants. Dyslipidemia significantly mediated the association between PM and GSD, with mediating proportions of 5.37%, 9.13%, and 7.66% in PM1, PM2.5, and PM10, respectively. ConclusionExposure to PM may relate to the increased risk of GSD in Chinese adults, especially among males, drinkers, and central obesity participants. Dyslipidemia may partially mediate the effect of PM-associated GSD development. Our results might provide epidemiological evidence for the progression of GSD related to PM and give new insights into GSD prevention and screening priorities.

Sex-specific differences in the associations of metabolic syndrome or components with gallstone disease in Chinese euthyroid population

In euthyroid population, it is uncertain whether there is sex-specific difference in the associations of metabolic syndrome (MetS) or its components with gallstone disease (GSD); in general population, MetS increases the risk of GSD. This was a cross-sectional study to investigate the sex-specific difference in the prevalence of MetS according to GSD status and the associations of MetS or its components with GSD in Chinese euthyroid population. The total prevalence of GSD was 8.1% (6.5% in men and 11.0% in women, with a significant difference (p < 0.001)). The total presence of MetS was 10.7% (12.1% in men and 8.2% in women,with a significant difference (p = 0.001)). The age-adjusted odds ratio of MetS for GSD was 2.775 in men (p < 0.001), 2.543 in women (p = 0.007) and 2.503 in the oveall samples (p < 0.001). Univariate analysis revealed that fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C) and thyroid-stimulating hormone (TSH) were associated with the prevalence of GSD. After adjustment for age, multivariate logistic regression analysis demonstrated that above three parameters were still significantly associated with the risk of GSD in general population; FPG and HDL-C but not TSH levels were significantly associated with the risk of GSD in men; and FPG and TSH levels but not HDL-C in women. Our study demonstrated that in euthyroid population, MetS appeared to be strongly associated with GSD regardless of sex, and FPG and TSH were two independent risk factors for GSD in men, while FPG and HDL-C in women.

Waist-to-height ratio for the prediction of gallstone disease among different obesity indicators.

Factors of metabolic syndrome such as obesity are well-known risk factors for gallstone disease (GSD). There are different indicators of obesity, including weight, body mass index, waist circumference, and waist-to-height ratio. The predictive ability of different obesity indicators for GSD remains unclear. To explore the most efficient predictor of GSD among the different anthropometric indicators of obesity. This population-based cross-sectional study included 2263 participants who completed a questionnaire detailing their demographics, medical history, and lifestyle between 2014 and 2017 in Taiwan. Blood samples were collected and physical examinations, including anthropometric measurements, were performed. Gallstone disease was ascertained using ultrasonography. Multivariate analyses were performed to identify independent risk factors for GSD. The overall prevalence of GSD was 8.8%. According to the multivariate analysis, individuals with a waist-to-height ratio ≥0.5 (odds ratio|odds ratios (OR)=1.65, 95% confidence interval (CI)=1.10-2.48, p=0.017) had an increased risk of GSD. Diabetes was the main risk factor for GSD in men (OR=2.06, 95% CI=1.17-3.65, p=0.013). Among women, waist-to-height ratio >0.5 (OR=1.76, 95% CI=1.03-3.02, p=0.040) and current hormone drug use (OR=2.73, 95% CI=1.09-6.84, p=0.033) were significant risk factors for gallstones. GSD was independently associated with central obesity and exogenous hormone intake in women. Among the anthropometric indicators used to assess central obesity, waist-to-height ratio was the most accurate predictor of GSD.

A mini-review of the associations between hypertension and risk of gallstone disease

A mini-review of the associations between hypertension and risk of gallstone disease

Risk factors for gallstone disease onset in Japan: Findings from the Shizuoka Study, a population-based cohort study.

In the research literature on factors associated with gallstones, large population-based cohort studies are rare. We carried out a study of this type to explore risk factors for the onset of gallstones. This study included Japanese participants aged 40-107 years who were followed prospectively from January 2012 to September 2020 using a dataset composed of two individually linked databases, one containing annual health checkup records and the other containing medical claims for beneficiaries of the National Health Insurance System and the Medical Care System for Elderly in the Latter Stage of Life in Shizuoka Prefecture, Japan. Among the 611,930 participants in the analysis set, 23,843 (3.9%) were diagnosed with gallstones during the observational period (median [max]: 5.68 [7.5] years). Multivariate analysis revealed that risk of gallstone disease was increased by male sex, cerebrovascular disease, any malignancy, dementia, rheumatic disease, chronic pulmonary disease, hypertension, and H. pylori-infected gastritis. These findings provide essential insights into the etiology of cholelithiasis and may contribute to efforts to reduce the incidence of the disease.

Physical activity and risk of gallstone disease: A Mendelian randomization study.

Objective: Given the association between physical activity and the reduced risk of gallstone disease as suggested in observational studies, a Mendelian randomization study was conducted to evaluate the causal nature of this association in genetic epidemiology. Study: Including self-reported and accelerometer-based physical activity traits, the independent genetic variants associated with physical activity were selected from the corresponding genome-wide association studies as instrumental variables. The summary-level data for gallstone disease were sourced from the UK Biobank (7,682 cases and 455,251 non-cases) and FinnGen consortium (23,089 cases and 231,644 non-cases). Then, two-sample Mendelian randomization analysis was conducted. Inverse-variance weight (IVW), weighted median, and Mendelian randomization-Egger regression were determined through Mendelian randomization analyses. To ensure the robustness of the results, sensitivity analyses were also carried out in the study. Results: The negative causality between the genetically predicted accelerometer-based "average acceleration" physical activity and the risk of gallstone disease was suggested in the UK Biobank study (p = 0.023, OR = 0.93, 95% CI: 0.87-0.99), and accelerometer-based "overall activity" physical activity and the risk of gallstone disease in the UK Biobank study (p = 0.017, OR = 0.38, 95% CI: 0.17-0.84). With accelerometer-based "average acceleration" physical activity negatively correlated with gallstone disease in the FinnGen consortium data (p = 0.001, OR = 0.94, 95% CI: 0.90-0.97). As for self-reported moderate-to-vigorous physical activity, however, there was no causality observed in both pieces of data. Conclusion: Our studies provide the evidence suggesting a casual association between physical activities and gallstone disease through analysis of genetic data. As indicated by the research results, there is a possibility that a higher level of physical activities could mitigate the risk of gallstone disease.

Complex impacts of gallstone disease on metabolic syndrome and nonalcoholic fatty liver disease.

Patients with gallstone disease (GSD) often have highly co-occurrence with metabolic syndrome (MetS) and Nonalcoholic fatty liver disease (NAFLD) both associated with insulin resistance (IR). Meanwhile, highly prevalence of NAFLD was found in patients who received cholecystectomy. However, the associations of GSD with MetS, NAFLD is inconsistent in the published literature. And risk of cholecystectomy on NAFLD is unclear. We searched the Medline EMBASE and WOS databases for literature that met our study topic. To be specific, studies with focus on associations between GSD and MetS/NAFLD, and risk evaluation on cholecystectomy and NAFLD incidence were enrolled for further analysis. The random effect model was used to calculate the combined relative ratio (RR) and odds ratio (OR)and 95% confidence interval (CI). Seven and six papers with focus on connections between GSD and NAFLD/MetS prevalence. Correspondingly, seven papers with focus on risk of cholecystectomy on NAFLD occurrence were also enrolled into meta-analysis. After pooling the results from individual study, patients with GSD had higher risk of MetS (OR:1.45, 95%CI: 1.23-1.67, I2 = 41.1%, P=0.165). Risk of GSD was increased by 52% in NAFLD patients (pooled OR:1.52, 95%CI:1.24-1.80). And about 32% of increment on NAFLD prevalence was observed in patients with GSD (pooled OR: 1.32, 95%CI:1.14-1.50). With regard to individual MetS components, patients with higher systolic blood pressure were more prone to develop GSD, with combined SMD of 0.29 (96%CI: 0.24-0.34, P<0.05). Dose-response analysis found the GSD incidence was significantly associated with increased body mass index (BMI) (pooled OR: 1.02, 95%CI:1.01-1.03) in linear trends. Patients who received cholecystectomy had a higher risk of post-operative NAFLD (OR:2.14, 95%CI: 1.43-2.85), P<0.05). And this impact was amplified in obese patients (OR: 2.51, 95%CI: 1.95-3.06, P<0.05). Our results confirmed that controls on weight and blood pressure might be candidate therapeutic strategy for GSD prevention. And concerns should be raised on de-novo NAFLD after cholecystectomy.

Addictive behavior and incident gallstone disease: A dose-response meta-analysis and Mendelian randomization study.

BackgroundPrevious studies have suggested associations between addictive behavior and gallstone disease (GSD) risk, yet conflicting results exist. It also remains unclear whether this association is causal or due to confounding or reverse associations. The present study aims to systematically analyze the epidemiological evidence for these associations, as well as estimate the potential causal relationships using Mendelian randomization (MR).MethodsWe analyzed four common addictive behaviors, including cigarette smoking, alcohol intake, coffee, and tea consumption (N = 126,906–4,584,729 participants) in this meta-analysis based on longitudinal studies. The two-sample MR was conducted using summary data from genome-wide associations with European ancestry (up to 1.2 million individuals).ResultsAn observational association of GSD risk was identified for smoking [RR: 1.17 (95% CI: 1.06–1.29)], drinking alcohol [0.84 (0.78–0.91)], consuming coffee [0.86 (0.79–0.93)], and tea [1.08 (1.04–1.12)]. Also, there was a linear relationship between smoking (pack-years), alcohol drinking (days per week), coffee consumption (cups per day), and GSD risk. Our MRs supported a causality of GSD incidence with lifetime smoking [1.008 (1.003–1.013), P = 0.001], current smoking [1.007 (1.002–1.011), P = 0.004], problematic alcohol use (PAU) [1.014 (1.001–1.026), P = 0.029], decaffeinated coffee intake (1.127 [1.043–1.217], P = 0.002), as well as caffeine-metabolism [0.997 (0.995–0.999), P = 0.013], and tea consumption [0.990 (0.982–0.997), P = 0.008], respectively.ConclusionOur study suggests cigarette smoking, alcohol abuse, and decaffeinated coffee are causal risk factors for GSD, whereas tea consumption can decrease the risk of gallstones due to the effect of caffeine metabolism or polyphenol intake.

The potential bidirectional association between Helicobacter pylori infection and gallstone disease in adults: A two-cohort study.

Previous studies have suggested that Helicobacter pylori (H. pylori) may act as a precipitating factor in gallstone formation, and the potential association between H. pylori infection and gallstone disease (GD) is still unclear and controversial. This study aimed to clarify the potential bidirectional relationship between H. pylori infection and GD. This retrospective cohort study was performed in a population that underwent health checkups at the hospital between 2013 and 2018. H. pylori infection status was evaluated by urea breath test (UBT), and GD was diagnosed via ultrasound. Cox regression and propensity score matching (PSM) were used. Among 1011 participants without H. pylori infection at baseline, 134 participants were infected with H. pylori. Among 1192 participants without gallstones or cholecystectomy at baseline, 60 participants developed gallstones or cholecystectomy. The hazard ratio (HR) (95% CI) for incident H. pylori infection comparing the GD versus the no GD group was 1.84 (1.19, 2.85). The age- and sex-adjusted HR (95% CI) for incident GD comparing H. pylori-positive subjects to H. pylori-negative subjects was 1.74 (1.01, 2.98). Consistent results were also found with PSM and multivariate analysis. This cohort study demonstrated a potential bidirectional association between H. pylori infection and GD, which provides a basis for indicating the risk of GD and implementing the clinical strategies for GD. For the prevention and treatment of GD, H. pylori infection should be carefully considered and evaluated.

Causal associations between changes in lipid profiles and risk of gallstone disease: a two-sample Mendelian randomization study.

BackgroundNonalcoholic fatty liver disease (NAFLD) has been linked to gallstone disease (GSD) in observational studies; however, the relationships between certain lipid profiles and GSD remain unclear.MethodsWe adopted a two-sample Mendelian randomization (MR) framework by applying different statistical methods to assess causalities between lipid profiles and GSD. We identified single-nucleotide polymorphisms (SNPs) for blood lipids and NAFLD from separate previous genome-wide association studies (GWASs).ResultsWe retrieved GSD SNPs attributed to 10,520 cases and 361,194 controls and validated our estimates using GWAS summary data from UK Biobank. We also performed sex-stratified analyses. Based on the summary estimates of 41, 59, 35, and 2 SNPs for low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), triglycerides (TGs), and NAFLD, respectively, we found no evidence of a causal relationship between genetically-predicted lipid profiles and GSD. The odds ratios were 0.995 for LDLC [95% confidence interval (CI): 0.994–0.998] per 0.98 mmol/L, 0.999 for HDLC (95% CI: 0.996–1.003) per 0.41 mmol/L, 0.997 for TGs (95% CI: 0.994–1.001) per 1 mmol/L, and 0.993 for NAFLD (95% CI: 0.984–1.003). No evidence of associations between lipid profile s and GSD in validation MR analyses or the sex-stratification analyses was noted.ConclusionsGenetically predicted hyperlipidemia or NAFLD is not causally associated with GSD.

GDF-15 as a Therapeutic Target of Diabetic Complications Increases the Risk of Gallstone Disease: Mendelian Randomization and Polygenic Risk Score Analysis.

Growth differentiation factor 15 (GDF-15) levels have been revealed as a robust biomarker for metformin use. We conducted Mendelian randomization (MR) analysis to explore the association between GDF-15 and gallstone disease to inform potential therapeutic effects targeting GDF-15. Four genetic variants associated with GDF-15 levels at p < 5 × 10–8 were selected as instrumental variables from a genome-wide association meta-analysis including 21,758 individuals. Two-sample MR analysis was conducted using summary-level data from UK Biobank (10,520 gallstone cases and 350,674 controls) and FinnGen consortium (19,023 gallstone cases and 195,144 controls). Polygenic risk score analysis using individual-level data in UK biobank was performed to complement the MR findings by examining the non-linearity of the association. Diabetic complications were taken as positive controls to validate the therapeutic effect of targeting GDF-15. Linear and nonlinear associations between genetically predicted GDF-15 levels and gallstones were estimated with stratification by the diabetic status. In the two-sample MR analysis, the odds ratio (OR) of gallstones was 1.09 (95% confidence interval (CI), 1.03–1.15; p = 0.001) for one standard deviation increase in genetically predicted GDF-15 levels in the meta-analysis of two datasets. Polygenic risk score analysis found this association to be U-shaped (p = 0.037). The observed association was predominantly seen in nondiabetic population (OR = 1.11, 95% CI: 1.01–1.21; p = 0.003). An inverse association between genetically predicted GDF-15 levels and diabetic complications (OR = 0.77, 95% CI: 0.62–0.96; p = 0.023) was observed, validating the potential therapeutic effects of targeting GDF-15 levels. This MR study indicates that the increased risk of gallstone disease should be taken into account when considering GDF-15 as a therapeutic target for diabetic complications.