Gallstone Disease In Patients Research Articles

Cost Effective Cholecystectemy in A Rural Tertiary Care Hospital

Background: Laparoscopic cholecystectomy is an accepted alternative to open cholecystectomy. This study was aimed to compare the results of laparoscopic and open cholecystectomy with respect to duration of operation, complications, hospital stay and cost.Materials and Methods: This was a prospective type of study. 200 patients of gallstone disease were randomly selected. 100 patients underwent laparoscopic cholecystectomy and 100 underwent open cholecystectomy from July 2014 to June 2015 in surgery units of Jahurul Islam Medical College Hospital. Data regarding age, sex, operation time, complications, hospital stay and total cost were collected from patient and from hospital record. Then we compared the data of laparoscopic and open cholecystectomy.Results: We found that mean operating time for laparoscopic cholecystectomy was 45 minutes and for open cholecystectomy was 60 minutes.There is no significant difference in incidence of complications between open and laparoscopic procedure. In our study, mean postoperative hospital stay for laparoscopic surgery was 3.5 days and in open cholecystectomy was 6 days. In this study total cost of laparoscopic surgery is less than open surgery though operation team charge is more in laparoscopic surgery.Conclusion: Laparoscopic cholecystectomy is a safe and cost effective alternative to open cholecystectomy.Anwer Khan Modern Medical College Journal Vol. 7, No. 1: Jan 2016, P 20-22

Outcome Analysis of Patients with Gallstone Disease Receiving Cholecystectomy: A Population-Based Cohort Study

Background/Aims: Cholecystectomy is generally performed to treat patients with gallstone disease (GSD) in clinical practice. The present study aimed to investigate whether type 2 diabetes mellitus (T2DM) may influence the overall survival of GSD patients. Methods: The National Health Insurance Research Database, a population-based registry data in Taiwan, was used to identify GSD patients from 2001 to 2008. The risk of cancers and effects of T2DM on the overall survival of GSD patients receiving cholecystectomy were estimated by hazards ratios (HRs) and 95% CIs using the Cox proportional hazard model. Results: Among 392,028 eligible GSD patients, 81,971 underwent cholecystectomy, whereas 310,057 did not. After cholecystectomy, the HR for developing cancer was 1.14. The HR for the overall survival was 0.74-fold lower for patients who underwent cholecystectomy than that for patients who did not. GSD patients without T2DM who underwent cholecystectomy (0.78-fold lower risk) had a longer survival, whereas those with T2DM had shorter survival (1.64-fold higher risk without cholecystectomy and 1.13-fold higher risk with cholecystectomy) compared with those without T2DM who did not undergo cholecystectomy. Conclusions: Our major findings suggest that T2DM may worsen the prognosis of GSD patients after cholecystectomy, which provides useful insight into the treatment of T2DM among GSD patients in clinical settings.

Impact of Biliary Calculi on the Liver

Gallstone is implicated for hepatocellular injury due to chronic extra hepatic large bile duct obstruction with or without repeated episodes of cholangitis. To study the liver changes in patients undergoing operative procedure for gallstone disease and to determine the relationship between severity of these changes with position of biliary calculus in biliary tree. Sixty patients who underwent operative procedure for gallstone disease between October 2013 and September 2015 were evaluated. The Liver Function Test (LFT) was done preoperatively and postoperatively. Intraoperative liver biopsy was taken. The histopathological changes of liver and their severity were noted. The most commonly observed liver function abnormality both in cholelithiasis (12.8%) and choledocholithiasis patients (50%) was increased alkaline phosphatase. Most commonly observed liver histology changes in patients with cholelithiasis was nonspecific reactive hepatitis (46.9%) and in choledocholithiasis was chronic cholestasis (50%). Patient with choledocholithiasis showed significant changes (p<0.001) in liver histopathology and LFT as compared to cholelithiasis. Patients with gallstone diseases developed significant functional as well as structural hepatic changes. Though the change was more significant in patient with choledocholithiasis compared to cholelithiasis, early operative procedure is recommended in all gallstone disease patients to prevent potential liver damage, irrespective of position of biliary calculi in biliary tree to prevent morbidities associated with it.

Cost-effectiveness of a new strategy to identify uncomplicated gallstone disease patients that will benefit from a cholecystectomy

BackgroundThe aim of this study was to determine the cost-effectiveness of a new strategy for the preoperative detection of patients that will likely benefit from a cholecystectomy, using simple criteria that can be applied by surgeons. Criteria for a cholecystectomy indication are: (1) having episodic pain; (2) onset of pain 1 year or less before the outpatient clinic visit.MethodsThe cost-effectiveness of the new strategy was evaluated against current practice using a decision analytic model. The incremental cost-effectiveness of applying criteria for a cholecystectomy for a patient with abdominal pain and gallstones was compared to applying no criteria. The incremental cost-effectiveness ratio (ICER) was expressed as extra costs to be invested to gain one more patient with absence of pain. Scenarios were analyzed to assess the influence of applying different criteria.ResultsThe new strategy of applying one out of two criteria resulted in a 4 % higher mean proportion of patients with absence of pain compared to current practice with similar costs. The 95 % upper limit of the ICER was €4114 ($4633) per extra patient with relief of upper abdominal pain. Application of two out of two criteria resulted in a 3 % lower mean proportion of patients with absence of pain with lower costs.ConclusionThe new strategy of using one out of two strict selection criteria may be an effective but also a cost-effective method to reduce the proportion of patients with pain after cholecystectomy.

Polymorphism and Expression Profile of Cholecystokinin Type A Receptor in Relation to Gallstone Disease Susceptibility.

In the present study, we investigated expression pattern of Cholecystokinin type A receptor (CCKAR) in relation to its commonly studied polymorphism (rs1800857, T/C) in gallstone disease (GSD) patients and controls. A total of 502 subjects (272 GSD and 230 controls) were enrolled, and genotyping was performed by evaluating restriction fragments of PstI digested DNA. For analyzing expression pattern of CCKAR in relation to polymorphism, gallbladder tissue samples from 80 subjects (GSD-55; control-25) were studied. Expression of CCKAR mRNA was evaluated by reverse transcriptase-PCR and confirmed using real-time PCR. Protein expression was evaluated by enzyme-linked immunosorbent assay. We observed significantly (p<0.0001) lower expression of CCKAR mRNA and protein in GSD tissues as compared with control. Significantly higher frequency of A1/A1 genotype (C/T transition) (p=0.0005) was observed for GSD as compared with control. Expression of CCKAR protein was found to be significantly lower (p<0.0001) in A1/A1 genotype as compared with other genotypes for GSD patients. Perhaps, this is the first report providing evidence of alteration in CCKAR expression in relation to its polymorphism elucidating the molecular pathway of the disease. Additional investigations with lager sample size are needed to confirm these findings.

P512. The prevalence and risk factors of gallstone disease in patients with ulcerative colitis

P512. The prevalence and risk factors of gallstone disease in patients with ulcerative colitis

The NPC1L1 Polymorphism 1679C>G Is Associated with Gallstone Disease in Chinese Patients.

Niemann Pick Type C1 Like 1 (NPC1L1) protein plays a key role in intestinal and hepatic cholesterol metabolism in humans. Genetic variation in NPC1L1 has been widely studied in recent years. We analyzed NPC1L1 single nucleotide polymorphisms in Chinese gallstone disease patients to investigate their association with gallstone disease. NPC1L1 mRNA expression was also measured in liver biopsies from patients with cholesterol gallstone disease and compared between genotypes. The G allele of the g1679C>G (rs2072183) polymorphism was significantly more prevalent in patients with gallstones compared with gallstone-free subjects. Moreover, patients carrying the G allele had lower hepatic NPC1L1 mRNA expression and higher biliary cholesterol (molar percentages) and cholesterol saturation index. Our study suggests that the G allele of the NPC1L1 polymorphism g1679C>G may be a positive marker of gallstone formation risk.

Histopathological spectrum of gallstone disease from cholecystectomy specimen in rural areas of West Bengal, India- an approach of association between gallstone disease and gallbladder carcinoma

Background: Gallstone disease (GSD) is a common health problem throughout the world and majority of this burden occurs in developing countries. Most of the gallbladder carcinoma (GBC) is associated with GSD but there is till deficit of information on this association. Beside this, there is no study on the spectrum of histopathological pattern of cholecystectomy specimens from GSD patients in rural areas of West Bengal of India. Methods: The study was carried out on GSD patients who were undergone for cholecystectomy at B.S. Medical College & Hospital of West Bengal over a period of three years from January 2013 to December 2015. Histopathological reports of cholecystectomy specimens were analyzed. Results: In the present study, total 786 GSD patients were included where 635 were female and 151 were male. Histopathological findings depicted that chronic cholecystitis was the most prevalent (79.8%) followed by acute-on-chronic cholecystitis (6.1%), cholesterolosis (2.9%) and xanthogranulomatous cholecystitis (1.7%) among the patients. Beside these, hyperplasia, metaplasia, dysplasia and GBC were observed in 2.0%, 4.7%, 2.2% and 0.6% of the patients respectively. The mean ages for patients with chronic cholecystitis, hyperplasia, metaplasia, dysplasia and carcinoma were 34.5, 37.2, 42.9, 43.9 and 53 years respectively. Study also showed that male GSD patients were more prone to pre-malignancy and malignancy (significant at 95% confidence limit). Conclusions: The study revealed that different types of histopathological features were present in the gallbladder of GSD patients where pre-malignant (hyperplasia, metaplasia and dysplasia) and malignant types were remarkable percentages though chronic cholecystitis was the commonest histopathological feature. Study also demonstrated that males with GSD were more prone to pre-malignancy and malignancy. Gradient ages may suggest that GBC was developed from cholecystitis to carcinoma via hyperplasia, metaplasia and dysplasia.

Upper gastrointestinal endoscopy prior to laparoscopic cholecystectomy: a clinical study at a tertiary care centre in central India

Background: Cholelithiasis is one of the most common problems encountered in surgery. It’s an immense challenge to discriminate between gastrointestinal symptoms due to gall stones or any other causes. These gastrointestinal symptoms have been related to gallstones but causal relationship has not been established yet, which is highly discouraging for the operating surgeon. An objectives of the study was to analyze the use of upper gastrointestinal endoscopy (UGE) as a pre-operative investigative tool in gallstone disease patients presenting with chronic dyspepsia. Methods: This prospective observational study was conducted on 216 patients at Department of Surgery at Aurobindo PG institute. The data collected from the patients included personal information, presenting signs and symptoms, investigations including USG, UGE finding, biopsy reports if present, medications, surgery details, any post-operative complications. Statistical analysis done by chi-square test. Results: Out of total patients, the mean age was 38.61 + 13.2 years. The male to female ratio was 1:3.one hundred and sixty (74.1%) patients had multiple stones. UGE showed a predominance of positive findings in group II with atypical symptoms than in group I (p-0.004). Therapeutic approach was changed in a total of 10 (4.6%), who were diagnosed with ulcer, malignancy and celiac disease. Cholecystectomy was performed in 206 (95.4%) patients. The relief rate is highest in group I with negative UGE than with group II. Conclusions: Besides its cost effectiveness, UGE is potentially helpful in reducing the incidence of postoperative persistence of symptoms. Thus UGE has a vital role in the initial evaluation and investigation of patients with symptomatic gallstone patients.

Is gallstone disease associated with inflammatory bowel diseases? A meta-analysis.

To investigate the association between inflammatory bowel disease (IBD) and gallstone disease (GD) by performing a meta-analysis. PubMed, Medline, Embase, Web of Science and the Cochrane Library were searched for relevant articles published between January 1980 and February 2015. All statistical analyses were performed using STATA 12.0. A fixed-effects model was adopted; heterogeneity was evaluated by χ(2) test and I(2) statistic; publication bias was assessed by Begg's and Egger's tests. Five studies qualified for inclusion in the meta-analysis. Patients with IBD had a significantly higher prevalence of GD than those in the control group [odds ratio (OR) 1.72, 95% confidence interval (CI) 1.40-2.12, P < 0.0001]. Subgroup analyses showed a significantly higher prevalence of GD in patients with Crohn's disease (CD) (OR 2.05, 95% CI 1.61-2.63, P < 0.0001). However, no significant difference in the prevalence of GD was observed between patients with ulcerative colitis (UC) and controls (OR 1.12, 95% CI 0.75-1.68, P = 0.585). Studies from Italy, Sweden and the UK revealed a higher prevalence of GD in patients with IBD. No heterogeneity (I(2) = 25.2%, P = 0.228) or publication bias was observed in our meta-analysis (Begg's test, P = 0.711; Egger's test, P = 0.805). Our meta-analysis suggests there is a trend towards higher prevalence of GD in IBD patients, and especially in patients with CD. More rigorous, large-scale multi-center studies are required to investigate the association between GD and IBD.

Effect of cholecystectomy on bile acid synthesis and circulating levels of fibroblast growth factor 19

Background and rationale for the study. FGF19/15 is a gut-derived hormone presumably governing bile acid (BA) synthesis and gallbladder (GB) refilling. FGF19 mRNA is present in human GB cholangiocytes (hGBECs); however, the physiological significance of GB-derived FGF19 remains unknown. We investigated whether hGBECs secrete FGF19 and the effects of cholecystectomy on serum FGF19 ([FGF19]s) and BA synthesis.Material and methods. FGF19 expression was assessed by qRT-PCRs and immunostaining in hGBECs and terminal ileum, and quantified in bile and serum by ELISA. Basal and BA (chenodexycholic acid, CDCA) induced FGF19 expression and secretion was analyzed in primary cultured hGBECs and GB-d1 cell line. Pre and postprandial serum changes in [FGF19]s, 7α-hydroxy-4-cholestene-3-one (C4, a marker of BA synthesis) and BA were evaluated in plasma of gallstone disease patients at baseline and after cholecystectomy.Results. FGF19 mRNA levels were -250-fold higher in hGBECs compared to distal ileum. GB bile contained -23-fold higher FGF19 levels compared to serum (p < 0.0001). CDCA induced dose-dependent expression and secretion of FGF19 in hGBECs and GB-d1 cells. Cholecystectomy increased plasma BA synthesis ≥ 2-fold (p < 0.0001), and altered the diurnal rhythm and significantly reduced [FGF19]s noon peak. BA serum levels, serum cholesterol and triglyceride content remained unchanged.Conclusions. In conclusion human GB cholangiocytes constitutively express and secrete high levels of FGF19 in a process regulated by BA. Resection of this organ doubles BA synthesis concomitantly with changes in [FGF19]s. These findings suggest a potential connection between GB cholangiocytes-derived FGF19 and BA metabolism that could lead to metabolic dysregulation following cholecystectomy.

Influence of ApoE and FABP2 polymorphisms and environmental factors in the susceptibility to gallstone disease

Background. Gallstone disease (GSD) is a common chronic disease in the Western hemisphere, yet environmental and genetic factors may be responsible for the variations in the prevalence of GSD among populations.Aim. To analyze the relationship of the ApoE and FABP2 polymorphisms with diet, physical activity and emotional health in patients with GSD from West Mexico.Material and methods. A total of 120 patients with GSD and 370 healthy subjects were enrolled. Anthropometric, biochemical, nutritional, clinical and physical activity parameters were measured. ApoE and FABP2 genotypes were assesed by PCR-RFLPs assays.Results: ApoE E3/E4 genotype and the ApoE E4 allele was highly prevalent among the GSD patients compared to the controls (32% vs. 12.0% and 22% vs. 8.4% respectively p < 0.01). Patients with the Apo E4 allele showed an upward trend of cholesterol levels compared to non-Apo E4 allele carriers (E4 186 ± 30 mg/dL; E3 143 ± 37 mg/dL; E2 129 ± 34 mg/dL). High triglyceride levels were associated with patients that were FABP2 Thr54 allele carriers (p < 0.05) but lacked association with GSD. This may be due to changes in dietary fats after GSD diagnosis, masking the clinical course of the disease. Sedentary lifestyle and negative emotions were detected in 83% and 63% of patients, respectively.Conclusion. These data suggest that the Apo E4 allele could confer genetic susceptibility for the development of GSD among the Mexican population. The Ala54Thr polymorphism of FABP2 was associated with high triglycerides levels, but not to GSD; suggesting that environmental factors modulate such susceptibility.

The concurrence of diabetes mellitus and gallstone disease

The article presents an update on the concurrence of diabetes mellitus (DM) and gallstone disease (GSD), on the mechanisms for the development of GSD in patients with type 2 DM (T2DM), on the risk factors of DM in GSD. The role of diabetic autonomic neuropathy of the gallbladder in the development of cholelithiasis is assessed in patients with T2DM. The impact of impaired secretion of neurohormones in the gastrointestinal tract in the development of DM in GSD is analyzed.

Контактное растворение желчных камней в эксперименте

In the experiment the possibility of using the dissolving mixture of octanoic acid-glycerol in a ratio of 1:1 for the treatment of gallstone disease in patients with high risk of operative treatment was justified. In in vitro experiments (n=107) using the proposed mixture, the time of dissolution of the bile concrements in the minute in terms of 1 mg mass of gallstones was identified: K=5,757 (n=51). The authors noted that the solubility of gallstones depends on their degree of mineralization. So, in a group with a low degree of concrements mineralization K&amp;#180;=4,256 (n=15), with an average K&amp;#180;=6,044 (n=17), high K&amp;#180;=6,971 (n=19). In the experiments in vivo on 35 adult rabbits after simulation of gallstone disease through cholecystostomy, the introduction of solvent mixture at the rate of 0.2 ml/kg of body weight once daily was carried out. Low mineralized concretions dissolved in all cases (after double injection), moderately mineralized – with the introduction of 3 days or more, and highly mineralized on the 4 day of treatment. After treatment, histologically and biochemically, pronounced toxic effect of the drug wasn’t detected. The use of contact litholyse in practice will significantly reduce the invasiveness of the treatment of patients with gallstone disease and reduce recovery time.

Prevalence of gallstone disease in patients with type 2 diabetes and the risk factors in North Indian population: a case control study.

Age, female sex, and obesity are considered to be risk factors for gallstone disease. The role of type 2 diabetes (T2D) in gallstone formation is still uncertain, and data in Indians is limited. This is a case-control study to determine the prevalence of gallstones (GS) in patients with T2D, risk factors, and the relative risk compared with subjects without diabetes, selected from the general population. Among 450 cases with T2D of a ≥2-year duration, 377 (88.8%) participated. Diagnosis of GS was made at ultrasonography and history of cholecystectomy for GS. Controls were selected from the general population and diabetes excluded by oral glucose tolerance test. Cases and controls were matched for age, gender, and body mass index (BMI). Gallstones were seen in 67 (17.7%) cases compared to 40 (5.8%) in controls (p = 0.001). Prevalence increased with increasing age with peak in the sixth decade (23.4% in cases and 4.4% in controls (p = 0.001) and was higher in women (27.9%) in cases and (7.8%) in controls, (p = 0.001). In univariate analysis, risk factors for GS included age, female sex, BMI, multiparity, family history of GS, and high triglycerides and cholesterol with low high-density lipoprotein cholesterol. In multivariate analysis, age, (relative risk [RR] 1.54, confidence interval [CI] 1.1-2.1), female sex (RR 1.6, CI 1.0-1.9), and BMI (RR 1.5, CI 1.3-2.5) were the independent risk factors in gallstone formation. Patients with T2D had higher probability of having GS compared to the general population. Increasing age, female sex, and higher BMI were independently associated with gallstone disease.

Gallstone Disease and the Risk of Stroke: A Nationwide Population-based Study

Gallstone disease (GD) and stroke share a number of risk factors including diabetes and hyperlipidemia. This nationwide population-based study was designed to estimate the risk of stroke after a diagnosis of GD. Data were obtained from the Taiwan National Health Insurance Research Database. A total of 135,512 patients with a diagnosis of GD and 271,024 age- and gender-matched non-GD control patients were included to assess the risk of stroke using Cox proportional hazard regression. During the study period (2000-2003), 12,234 (153.67/10,000 person-years) strokes occurred among the GD patients, and 20,680 (114.83/10,000 person-years) among the controls. The diagnosis of GD carried a higher risk of developing ischemic and hemorrhagic stroke, with a hazard ratio (HR) of 1.28 and 1.33 (95% confidence interval [CI], 1.25-1.31 and 1.25-1.41, both P<.0001), respectively. Stroke risk was increased in both genders but at a higher rate in younger age. The GD group had significantly higher prevalence rate of comorbidities that are known stroke risk factors, including hypertension, diabetes, and coronary artery disease. Stroke risk was higher in the GD group with or without any of these comorbidities. In this population-based longitudinal follow-up study, GD carried a significantly higher stroke risk, particularly for younger age with or without stroke risk factors. Stroke preventive measures maybe needed for patients with GD, especially those of younger age and with stroke risk factor(s).

Association of adrenergic receptor gene polymorphisms in gallbladder cancer susceptibility in a North Indian population

Gallbladder cancer (GBC), the most common gastrointestinal and biliary tract malignancy, often coincides with gallstone disease (GSD). The genetic variants of adrenergic receptor (ADR) have been previously reported to be associated with hypomotility disorder of cardiovascular system and GSD. Since GSD may function as GBC precursor, the present study aimed to investigate the association of common functional genetic variants of ADRA2A C-1291G, ADRβ3 T190C or Trp64Arg, and ADRβ1 C1165G or Arg389Gly with GBC and GSD susceptibility. The present study included a total of 400 histologically confirmed GBC, 230 GSD, and 268 healthy controls. The ADRA2A C-1291G, ADRβ3 T190C, and ADRβ1 C1165G polymorphisms were determined by PCR-RFLP. Statistical analysis was performed by using SPSS version 16. ADRβ3 T190C polymorphism was significantly associated with increased risk of GBC (CT: Pcorr = 0.015, OR 2.87; CC: Pcorr = 0.038, OR 10.33; C allele: Pcorr = 0.014, OR 2.7; CT + CC: Pcorr = 0.017, OR 3.05). These associations existed even after gallstone and gender stratification. Similarly, ADRβ3 T190C polymorphism was also associated with GSD risk, though limited only to female GSD patients. In contrary, ADRA2A C-1291G conferred a marginally increased risk only in GSD patients. ADRβ1 C1165G polymorphism was not associated with GBC and GSD susceptibility when compared to controls. ADRβ3 T190C polymorphism is significantly associated with GBC and GSD susceptibility. The ADRβ3 T190C may be involved in the pathophysiology of GBC by both gallstone-dependent pathway and by some other independent mechanisms.

Diet and Nutritional Factors Related to Symptomatic Gallstone Disease in Women

Background: Gallstone Disease (GD) results from the interaction of genetic predisposition and environmental factors such as physical activity, diet and food habits that are characteristic of each culture. Female gender, aging, obesity and insulin resistance are strongly associated to gallstone formation. Female Mexican population presents high prevalence of obesity and GD. Hence our aim was to establish the relationship between GD, dietary constituents and nutritional factors in women with symptomatic cholelithiasis. Methods: We performed a case-control study in 93 women with symptomatic gallstones and 95 controls. Evaluations included clinical aspects, anthropometry, 24-hours dietary recalls, food habits and physical exercise. Results: Family history of GD was present in 53% of GD patients, 54% showed insulin resistance. GD women, compared to controls, had more overweight and obesity (83% vs. 69%), higher waist-to-hip ratio (0.869 ± 0.06 vs. 0.838 ± 0.063, p=.001), consumed lesser meals /day (2.91 ± 0.76 vs. 3.61 ± 0.81 p<0.001), ingested more energy (2186 kcal vs. 1366 kcal p<0.001), more total fat (65 vs. 43 g/day; p<0.001) and more portions of simple sugars per 1000 kcal (2.5 vs. 2.0 p=0.025). Fewer GD women consumed dietary fiber recommended allowance (3 vs. 25% p<0.0001). Overnight fasting periods were longer in the GD group. Most patients and controls had a sedentary life style. Conclusion: Obesity, abdominal adiposity, insulin resistance and nutritional factors such as excessive intake of total energy, total fat, simple sugar and long fasting periods; constitute risk factors for gallstone formation. Meanwhile, adequate dietary fiber intake is a protective factor in this population of Mexican women.

Significantly Increased Risk of Cardiovascular Disease among Patients with Gallstone Disease: A Population-Based Cohort Study

ObjectiveTo investigate whether gallstone disease (GD) increases the risk of developing cardiovascular disease (CVD) in a large population-based cohort.MethodsA study population including 6,981 patients with GD was identified from The Taiwan National Health Insurance Research Database between 2004 and 2005. GD patients were defined as patients with principal discharge diagnoses of cholelithiasis using the ICD-9-CM code 574. 27,924 patients without GD were randomly selected and matched for age and gender. All patients were followed for 6 years or until diagnosis for CVD. Cox proportional hazards regression model was used to assess the risk of developing CVD with adjustment for age, gender and co-morbid conditions.ResultsDuring the six years follow-up period, 935 patients with GD and 2,758 patients without GD developed CVD. Patients with GD had an elevated risk of CVD (HR, 1.32; 95% CI, 1.22-1.43) when compared with those without GD. Similar relationship was observed when CVD was categorized i.e. stroke (HR, 1.15; 95% CI, 1.01-1.32), coronary heart disease (HR, 1.42; 95% CI, 1.28-1.58) and heart failure (HR, 1.31; 95% CI, 1.00-1.73). When GD was classified according to the level of severity, using patients without GD as reference, the risks of CVD were elevated in patients with non-severe GD (HR, 1.34; 95% CI, 1.24-1.46) as well as those with severe GD (HR, 1.20, 95% CI, 1.02-1.40), after adjusting for age, gender and comorbidities. In age-stratified analysis, patients aged 18-40 years with GD were at higher risk of developing CVD (HR, 1.42; 95% CI, 1.09-1.84) than older GD patients.ConclusionThis study found an increased risk of CVD in patients diagnosed with GD. The excess risk was particularly high in younger GD patients. Prevention of GD could help reduce the risk of developing CVD, and the better effect could be achieved for the younger age groups.

Single nucleotide polymorphism rs3732860 in the 3′‐untranslated region of CYP8B1 gene is associated with gallstone disease in Han Chinese

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. 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. 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. 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.