The influence of RS738409 I148M polymorphism of patatin-like phospholipase domain containing 3 gene on the susceptibility of non-alcoholic fatty liver disease

We aimed to elucidate the frequency of polymorphic genotypes and alleles of patatin-like phospholipase domain containing 3 rs738409 polymorphism and its possible associations with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis in a cohort from Turkey.We enrolled 200 patients diagnosed with NAFLD and genotyped for rs738409 I148M polymorphism by real-time polymerase chain reaction, particularly by melting curve analysis. SPSS analysis software was used for statistical significance. Continuous variable values were expressed as mean ± standard deviation. Significant statistical level was chosen as p = 0.05.Our results demonstrate in a cohort from Turkey that rs738409 C > G polymorphism (I148M) of patatin-like phospholipase domain containing 3 gene is significantly able to affect individuals to have NAFLD in unadjusted regression model.Consistent with the previous studies in other populations, our study group showed a significantly higher risk of having NAFLD in unadjusted regression model but not in the adjusted model indicating that non-genetic factors such as age and sex may be responsible for the association. However, independent studies need to validate our findings with a larger group of NAFLD patients, as well as in different ethnic cohorts.     

Apolipoproteins and liver parameters optimize cardiovascular disease risk-stratification in nonalcoholic fatty liver disease

BackgroundAdvanced Non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease (CVD).AimWe determine whether combinations of ultrasound graphic steatosis grades, fibrosis scores and apolipoprotein levels add value to CVD risk prediction in NAFLD patients.MethodsThe retrospective cohort study enrolled 10,453 individuals (3519 NAFLD; 6934 non NAFLD) from 2004 to 2018. Hepatic ultrasound measurements, lipid and apolipoprotein profiles, Fibrosis-4 and the NAFLD fibrosis scores (NFS) were assessed. The primary outcome included both clinical and subclinical CVD.ResultsDuring 116-month follow-up period, there were 957 clinical and 752 subclinical CVD events. NAFLD patients had a higher incidence of CVD than non NAFLD patients as the steatosis degree, NFS, and FIB4 scores increased (25.1% vs 11.9%, Log Rank: p < 0.001). For the lipid and apolipoprotein profiles excluding triglyceride or ApoE, subjects with varied steatosis severity in the upper two tertiles had different risk of CVD (p for interaction < 0.001). A nomogram model combination of Framingham Risk Score (FRS), NFS and apolipoprotein profiles presented a higher AUC than FRS in a time-dependent ROC curve (0.816 vs 0.752, p < 0.001).ConclusionThe novel risk score considering ultrasonography-defined steatosis grades, non-invasive liver fibrosis scores and apolipoprotein profiles accurately predicted the 10-year risk of CVD.     

Hepatic steatosis and metabolic risk factors among patients with chronic hepatitis B: The multicentre,prospective CAP-Asia study

We aimed to compare the severity of liver disease, metabolic profile and cardiovascular disease (CVD) risk of chronic hepatitis B (CHB) patients with and without hepatic steatosis and patients with non-alcoholic fatty liver disease (NAFLD). Patients with NAFLD and CHB were prospectively enrolled from 10 Asian centres. Fibroscan was performed for all patients and hepatic steatosis was defined based on controlled attenuation parameter >248 dB/m. CVD risk was assessed using the Framingham risk score. The data for 1080 patients were analysed (67% NAFLD, 33% CHB). A high proportion (59%) of CHB patients had hepatic steatosis. There was a significant stepwise increase in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, controlled attenuation parameter and liver stiffness measurement, from CHB patients without hepatic steatosis to CHB patients with hepatic steatosis to NAFLD patients (p < 0.001 for all comparisons). There was a significant stepwise increase in the proportion of patients with metabolic syndrome and in CVD risk, with very high or extreme CVD risk seen in 20%, 48% and 61%, across the groups (p < 0.001 between CHB patients with and without hepatic steatosis and p < 0.05 between CHB patients with hepatic steatosis and NAFLD patients). In conclusion, there was a high proportion of CHB patients with hepatic steatosis, which should be diagnosed, as they may have more severe liver disease, so that this and their metabolic risk factors can be assessed and managed accordingly for a better long-term outcome     

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.     

Linked PNPLA3 polymorphisms confer susceptibility to nonalcoholic steatohepatitis and decreased viral load in chronic hepatitis B

AIM: To investigate the association of PNPLA3 polymorphisms with concurrent chronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD).METHODS: A cohort of Han patients with biopsy-proven CHB, with or without NAFLD (CHB group, n = 51; CHB + NAFLD group, n = 57), and normal controls (normal group, n = 47) were recruited from Northern (Tianjin), Central (Shanghai), and Southern (Zhangzhou) China. Their PNPLA3 polymorphisms were genotyped by gene sequencing. The association between PNPLA3 polymorphisms and susceptibility to NAFLD, and clinical characteristics of NAFLD were evaluated on the basis of physical indices, liver function tests, glycolipid metabolism, and histopathologic scoring. The association of PNPLA3 polymorphisms and hepatitis B virus (HBV) load was determined by the serum level of HBV DNA.RESULTS: After adjusting for age, sex, and body mass index, we found that four linked single nucleotide polymorphisms (SNPs) of PNPLA3, including the rs738409 G allele (CHB + NAFLD group vs CHB group: odds ratio [OR] = 2.77, 95% confidence interval [CI]: 1.18-6.54; P = 0.02), rs3747206 T allele (CHB + NAFLD group vs CHB group: OR = 2.77, 95%CI: 1.18-6.54; P = 0.02), rs4823173 A allele (CHB + NAFLD group vs CHB group: OR = 2.73, 95%CI: 1.16-6.44; P = 0.02), and rs2072906 G allele (CHB + NAFLD group vs CHB group: OR = 3.05, 95%CI: 1.28-7.26; P = 0.01), conferred high risk to NAFLD in CHB patients. In patients with both CHB and NAFLD, these genotypes of PNPLA3 polymorphisms were associated with increased susceptibility to nonalcoholic steatohepatitis (NASH) (NAFLD activity score ≥ 3; P = 0.01-0.03) and liver fibrosis (> 1 Metavir grading; P = 0.01-0.04). As compared to those with C/C and C/G at rs738409, C/C and C/T at rs3747206, G/G and G/A at rs4823173, and A/A and A/G at rs2072906, patients in the CHB + NAFLD group with G/G at rs738409, T/T at rs3747206, A/A at rs4823173, and G/G at rs2072906 showed significantly lower serum levels of HBV DNA (P < 0.01-0.05).CONCLUSION: Four linked SNPs of PNPLA3 (rs738409, rs3747206, rs4823173, and rs2072906) are correlated with susceptibility to NAFLD, NASH, liver fibrosis, and HBV dynamics in CHB patients.     

Silymarin in non alcoholic fatty liver disease

AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD).METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory parameters were assayed after 3 mo of a restricted diet and before silymarin treatment (twice a day orally). The brightness of liver echography texture (hepatorenal ratio brightness) was also defined at same time. These evaluations were repeated after 6 mo of treatment.RESULTS: Serum levels of some metabolic and anti-inflammatory data nonsignificantly lowered after 6 mo of silymarin. On the contrary, Steato test, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase were significantly (P < 0.001) reduced. Instead, the AST/ALT ratio unchanged. Finally, the hepatorenal brightness ratio, as an index of hepatic steatosis, significantly (P < 0.05) dropped.CONCLUSION: The obtained results indicate that silymarin appears to be effective to reduce the biochemical, inflammatory and ultrasonic indices of hepatic steatosis. Some parameters indicative of early stage of atherosclerosis were also lowered.     

The HSD17B13 rs72613567 variant is associated with lower levels of albuminuria in patients with biopsy-proven nonalcoholic fatty liver disease

Background and aimsSeveral susceptibility gene variants predisposing to nonalcoholic fatty liver disease (NAFLD) have been identified in chronic kidney disease (CKD). Evidence supports that 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) rs72613567 plays a role in NAFLD development by affecting lipid homeostasis. Since lipid droplets may accumulate in the kidneys and contribute to renal injury, we investigated the association between the HSD17B13 rs72613567 variant and markers of renal function/injury in NAFLD.Methods and resultsWe measured estimated glomerular filtration rate (eGFR), urinary/serum neutrophil gelatinase-associated lipocalin (NGAL), and urinary albumin-to-creatinine ratio (u-ACR) in individuals with biopsy-proven NAFLD. Multivariable regression analyses were undertaken to examine the associations between the HSD17B13 rs72613567 variant and markers of renal function/injury. Individuals were stratified by HSD17B13 rs72613567 genotypes into ?/?, A/- and A/A groups. HSD17B13 rs72613567 genotypes were not significantly associated with eGFR and urinary/serum NGAL levels. Conversely, the prevalence of abnormal albuminuria in the A/- + A/A group was lower than in the ?/? group (4.92% vs. 19.35%, p = 0.001). Additionally, the mean u-ACR levels were lower among carriers of the A/- or A/A genotypes with coexisting hypertension or diabetes, than among those with the ?/? genotype. The risk of abnormal albuminuria (adjusted-odds ratio 0.16, p = 0.001) remained significantly lower in the A/- + A/A group after adjustment for established renal risk factors and histologic severity of NAFLD.ConclusionHSD17B13 rs72613567: A allele is associated with a lower risk of having abnormal albuminuria, but not with lower eGFR or urinary/serum NGAL levels, in patients with biopsy-proven NAFLD.     

Association between APE1 rs1760944 and rs1130409 polymorphism with prostate cancer risk: A systematic review and meta-analysis

Background:Recently, some studies have suggested that the association of apurinic/apyrimidinic endonuclease 1 (APE1) gene polymorphism with prostate cancer (PCa) risk, but there are still some controversies. Hence, we elaborated the relationship between APE1 rs1760944 and rs1130409 gene and PCa risk through systematic literature review and meta-analysis.Methods:As of March 2020, EMBASE, PubMed, the Cochrane Library, Science Direct/Elsevier, MEDLINE and CNKI were used for systematic literature retrieval to investigate the correlation between APE1 rs1760944 and rs1130409 gene polymorphism with PCa risk. Meta-analysis was performed using Review Manager and Stata software.Results:Seven studies were distinguished, consists of 1769 cases of PCa patients and 2237 normal controls. Our results illustrated that there are significant correlation between the APE1 rs1760944 gene polymorphism and PCa in all genetic models (P < .05). The combined odds ratios and 95% confidence intervals were as follows: Additive model (ORs 0.62, 95%, CI [0.39, 0.97]); Codominant model (ORs 0.74, 95% CI [0.58, 0.95]); Dominant model (ORs 0.75, 95%, CI [0.59, 0.95]); Recessive model (ORs 0.63, 95% CI [0.41, 0.96]); Allele model (ORs 0.78, 95% CI [0.65, 0.94]). There also have significant associations between APE1 rs1130409 polymorphisms and PCa in all genetic models (P < .05). The combined odds ratios and 95% confidence intervals were as follows: Additive model (ORs 1.37, 95%, CI [1.01, 1.85]); Codominant model (ORs 1.21, 95% CI [1.01, 1.44]); Dominant model (ORs 1.33, 95%, CI [1.02, 1.73]); Recessive model (ORs 1.74, 95% CI [1.06, 2.85]); Allele model (ORs 1.14, 95% CI [1.00, 1.29]).Conclusion:This study suggests that APE1 rs1760944 polymorphisms might be a protective factor of PCa, and APE1 rs1130409 is suggested to be a risk factor of PCa. APE1 rs1760944 and rs1130409 polymorphisms may be used in the risk assessment of PCa.     

Hypolactasia is associated with insulin resistance in nonalcoholic steatohepatitis

AIM To assess lactase gene(LCT)-13910CT polymorphisms in Brazilian non-alcoholic fatty liver disease(NAFLD) and nonalcoholic steatohepatitis(NASH) patients in comparison with healthy controls.METHODS This was a transverse observational clinical study with NAFLD patients who were followed at the Hepatology Outpatient Unit of the Hospital das Clínicas, S?o Paulo, Brazil. The polymorphism of lactase non-persistence/lactase persistence(LCT-13910CT) was examined by PCR-restriction fragment length polymorphism technique in 102 liver biopsy-proven NAFLD patients(steatosis in 9 and NASH in 93) and compared to those of 501 unrelated healthy volunteers. Anthropometric, clinical, biochemical and liver histology data were analyzed. Continuous variables were compared using the t or Mann-Whitney tests, and categorical data were compared with the Fisher's exact test. Univariate logistic regression and multivariate logistic regression adjusted for gender and age were performed.RESULTS No differences in the LCT-13910 genotype frequencies were noted between the NAFLD patients(66.67% of the patients with steatosis were CC, 33.33% were CT, and none were TT; 55.91% of the patients with NASH were CC, 39.78% were CT, and 4.3% were TT; P = 0.941) and the healthy controls(59.12% were CC, 35.67% were CT, and 5.21% were TT) or between the steatosis and NASH patients. That is, the distribution of the lactase non-persistence/lactase persistence polymorphism(LCT-13910CT) in the patients with NAFLD was equal to that in the general population. In the NASH patients, the univariate analysis revealed that the lactase nonpersistence(low lactase activity or hypolactasia) phenotype was associated with higher insulin levels(23.47 ± 15.94 μU/m L vs 15.8 ± 8.33 μU/m L, P = 0.027) and a higher frequency of insulin resistance(91.84% vs 72.22%, P = 0.02) compared with the lactase persistence phenotype. There were no associations between the LCT genotypes and diabetes(P = 0.651), dyslipidaemia(P = 0.328), hypertension(P = 0.507) or liver histology in these patients. Moreover, in the NASH patients, hypolactasia was an independent risk factor for insulin resistance even after adjusting for gender and age [OR = 5.0(95%CI: 1.35-20; P = 0.017)].CONCLUSION The LCT-13910 genotype distribution in Brazilian NAFLD patients was the same as that of the general population, but hypolactasia increased the risk of insulin resistance in the NASH patients.     

Association of adiponectin gene polymorphisms and additional gene-gene interaction with nonalcoholic fatty liver disease in the Chinese Han population

Purpose

To investigate the association between the single nucleotide polymorphisms (SNPs) of the adiponectin gene and nonalcoholic fatty liver disease (NAFLD) as well as the impact of the interaction of multiple SNPs on NAFLD risk, based on a Chinese population study.

Methods

A total of 612 subjects (411 male, 201 female) were selected, including 302 NAFLD patients and 310 controls. Three SNPs were selected for genotyping in the case-control study: rs266729, rs822393, and rs1501299. A logistic regression model was used to examine the interaction between the SNPs and NAFLD. The odds ratio (OR) and 95 % confidence interval (95 % CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the interaction among SNPs.

Results

Logistic analysis showed a significant association between genotypes of variants in rs266729 and rs822393 and increased NAFLD risk. The carriers of the homozygous mutant of two SNP polymorphisms revealed increased NAFLD risk compared to those with wild-type homozygotes; ORs (95 % CI) were 1.31 (1.14–1.81) (p = 0.001) and 1.18 (1.05–1.71) (p = 0.005), respectively. There was a significant two-locus model (p = 0.0010) involving rs266729 and rs822393, indicating a potential gene-gene interaction between rs266729 and rs822393. Overall, the two-locus models had a cross-validation consistency of 10 and testing accuracy of 62.17 %. Subjects with the CG or GG and CT or TT genotype have the highest NAFLD risk compared to subjects with the CC-CC genotype; the OR (95 % CI) was 2.52 (1.31–3.82), p < 0.001, after covariate adjustment.

Conclusions

Our results support an important association of the rs266729 (?11377 G/C) and rs822393 (?4522 C/T) polymorphism with increased risk of NAFLD. The interaction analysis showed a combined effect of rs266729 and rs822393 on NAFLD.

     

Polymorphism in microRNA-196a2 contributes to the risk of cardiovascular disease in type 2 diabetes patients

AimsTo investigate the effect of the microRNA-196a2 gene polymorphism (rs11614913) on risk of cardiovascular disease in type 2 diabetes patients.MethodsWe examined 920 patients with diabetes and 834 healthy controls. All subjects were genotyped for the miRNA-196a2 SNP by polymerase chain reaction (PCR) and restriction analysis.ResultsThe genotype distribution among controls and patients was in Hardy–Weinberg equilibrium (p = 0.227 and 0.308, respectively). The frequency of the T allele was lower in patients than in controls (p = 0.044). The odds ratio 0.66 (95% CI 0.54–0.79) suggests an association of the T allele with decreased risk of T2DM. For the main purpose of the study, T2DM patients were stratified into patients with CVD and those without it. The T allele and TT genotype were significantly more frequent in patients with CVD compared to those without CVD (p = 0.013, p < 0.001, respectively). The odds ratio for the T allele in the CVD + subgroup vs. CVD − was 1.76 (1.35–2.30), p < 0.0001, mostly due to the overrepresentation of TT homozygotes. The highest risk of development of CVD was observed in the additive model for TT homozygotes (OR 3.33, 95% CI 2.05–5.42, p < 0.0001).ConclusionOur findings suggest that miRNA-196a2 T/C polymorphism (rs11614913) is associated with an increased risk of CVD in type 2 diabetes patients. This provides further insights on pathogenesis of cardiovascular disease in type 2 diabetes patients.     

Meta-analysis of prophylactic corticosteroid use in post-ERCP pancreatitis

Background

Genetic factors as well as environmental factors are important in the development of NAFLD and in this study we investigated associations between polymorphisms of peroxisome proliferators-activated receptor γ coactivator 1α polymorphism (PPARGC1A) and NAFLD.

Aims

We recruited 115 patients with biopsy-proven NAFLD, 65 with NASH and 50 with simple steatosis, and 441 healthy control subjects and investigated 15 SNPs of PPARGC1A.

Results

SNP rs2290602 had the lowest p value in the dominant mode (p = 0.00095), and the odds ratio for NAFLD (95% CI) was 2.73 (1.48 – 5.06). rs2290602 was significantly associated with NAFLD even when the most conservative Bonferroni's correction was applied (p = 0.0143). The frequency of the T allele of rs2290602 was significantly higher in the NASH patients than in the control subjects (p = 0.00093, allele frequency mode), and its frequency in the NASH patients tended to be higher than in the simple steatosis patients (p = 0.09). The results of the real-time RT-PCR study showed that intrahepatic mRNA expression of PPARGC1A was lower in the TT group than in the GG or GT group at SNP rs2290602 (p = 0.0454).

Conclusion

This is the first study to demonstrate a significant association between genetic variations in PPARGC1A and NAFLD. This finding suggested that PPARGC1A polymorphism and lower expression of PPARGC1A mRNA in the liver are an important genetic contribution to etiology of NAFLD.     

Association Between LYPLAL1 rs12137855 Polymorphism With Ultrasound-Defined Non-Alcoholic Fatty Liver Disease in a Chinese Han Population

Background:

Recent genome-wide association studies (GWAS) identified that gene Lysophospholipase-like 1 (LYPLAL1) rs12137855 associated with non-alcoholic fatty liver disease (NAFLD). No research has been performed regarding the association between LYPLAL1 and NAFLD in China.

Objectives:

The aim of the present study was to investigate the association between the gene LYPLAL1 rs12137855 and NAFLD, and the effect on serum lipid profiles in a Chinese Han population.

Patients and Methods:

LYPLAL1 rs12137855 gene was genotyped in 184 patients with NAFLD and 114 healthy controls using sequencing and polymerase chain reaction analysis (PCR). We tested serum lipid profiles using biochemical methods.

Results:

No significant differences in genotype and allele frequencies of LYPLAL1 rs12137855 was found between the NAFLD group and the controls group (P > 0.05). Subjects with the variant LYPLAL1 rs12137855 CC genotype had a higher mean weight, body mass index (BMI) and low density lipoprotein (LDL).

Conclusions:

Our results showed for the first time that LYPLAL1 gene is not associated with a risk of NAFLD development in the Chinese Han population. The variant carriers of overall subjects significantly increased weight, BMI and LDL.     

Acute cardiovascular hospitalizations and illness severity before and during the COVID‐19 pandemic

BackgroundCardiovascular disease (CVD) hospitalizations declined worldwide during the COVID‐19 pandemic. It is unclear how shelter‐in‐place orders affected acute CVD hospitalizations, illness severity, and outcomes.HypothesisCOVID‐19 pandemic was associated with reduced acute CVD hospitalizations (heart failure [HF], acute coronary syndrome [ACS], and stroke [CVA]), and worse HF illness severity.MethodsWe compared acute CVD hospitalizations at Duke University Health System before and after North Carolina''s shelter‐in‐place order (January 1–March 29 vs. March 30–August 31), and used parallel comparison cohorts from 2019. We explored illness severity among admitted HF patients using ADHERE (“high risk”: >2 points) and GWTG‐HF (“>10%”: >57 points) in‐hospital mortality risk scores, as well as echocardiography‐derived parameters.ResultsComparing hospitalizations during January 1–March 29 (N = 1618) vs. March 30–August 31 (N = 2501) in 2020, mean daily CVD hospitalizations decreased (18.2 vs. 16.1 per day, p = .0036), with decreased length of stay (8.4 vs. 7.5 days, p = .0081) and no change in in‐hospital mortality (4.7 vs. 5.3%, p = .41). HF hospitalizations decreased (9.0 vs. 7.7 per day, p = .0019), with higher ADHERE (“high risk”: 2.5 vs. 4.5%; p = .030), but unchanged GWTG‐HF (“>10%”: 5.3 vs. 4.6%; p = .45), risk groups. Mean LVEF was lower (39.0 vs. 37.2%, p = .034), with higher mean LV mass (262.4 vs. 276.6 g, p = .014).ConclusionsCVD hospitalizations, HF illness severity, and echocardiography measures did not change between admission periods in 2019. Evaluating short‐term data, the COVID‐19 shelter‐in‐place order was associated with reductions in acute CVD hospitalizations, particularly HF, with no significant increase in in‐hospital mortality and only minor differences in HF illness severity.     

Correlation between lncRNA SNHG16 gene polymorphism and its interaction with environmental factors and susceptibility to colorectal cancer

Objective:To study the relationship between long-chain non-coding RNA small nucleolar RNA host gene 16 (lncRNA SNHG16) polymorphisms and its interaction with environmental factors and susceptibility to colorectal cancer (CRC).Methods:Sanger sequencing was used to analyze genotypes of lncRNA SNHG16 gene rs7353, rs8038, and rs15278 sites. Multifactor dimensionality reduction was used to analyze interactions between lncRNA SNHG16 gene rs7353, rs8038, rs15278 sites, and environmental factors. Haploview 4.1 software was used to analyze linkage disequilibrium of lncRNA SNHG16 gene rs7353, rs8038, and rs15278 sites. Quantitative real-time polymerase chain reaction was used to analyze plasma lncRNA SNHG16 levels of CRC patients and control subjects.Results:Variation of the lncRNA SNHG16 gene rs7353 site A>G variation was associated with decreased CRC susceptibility (Odds ratio [OR] = 0.50, 95% confidence interval [CI]: 0.40–0.62, P < .01). The rs8038 site G>A and rs15278 site A>G variation were associated with increased CRC susceptibility (OR = 1.87, 95% CI: 1.47–2.36, P < .01). The rs15278 site G>A variation was associated with increased CRC susceptibility (OR = 2.24, 95% CI: 1.61–3.11, P < .01). Interaction combinations featuring age, rs7353, rs8038, and rs15278 single nucleotide polymorphism are 13.53 times more susceptible to CRC than other interactions (95% CI: 9.43–19.41, P < .01). The rs15278, rs8038, and rs7353 site AGA haplotypes were significantly associated with a decreased CRC risk (OR = 0.65, 95% CI: 0.48–0.88, P = .01), AAG haplotypes were significantly associated with an increased CRC risk (OR = 2.00, 95% CI: 1.27–3.17, P < .01). High lncRNA SNHG16 expression was associated with tumor progression in CRC patients (χ² = 8.85, P = .03). The rs7353 site A>G variation caused a significant decrease in plasma lncRNA SNHG16 level (P < .01), while the rs8038 site G>A variation and rs15278 site A>G variation resulted in increased plasma lncRNA SNHG16 levels.Conclusion:Polymorphisms of lncRNA SNHG16 gene rs7353, rs8038, rs15278 loci and their interaction with age are significantly associated with CRC susceptibility.     

CAV1 rs7804372 (T29107A) polymorphism might be a potential risk for digestive cancers: A protocol for systematic review and meta analysis

Background:Caveolin-1 (CAV1) is an essential structural component of caveolae, regulates cellular processes through complex cellular signaling pathways, and influences tumorigenicity. However, the role of the CAV1 (rs7804372) polymorphism in digestive cancers remains inconclusive. The meta-analysis was performed to evaluate the effect of CAV1 polymorphism on digestive cancer susceptibility and to provide a basis for precise treatment.Methods:The databases of PubMed, EMBASE, Google Scholar and CNKI were used to retrieve the published studies on CAV1 (rs7804372) polymorphism and susceptibility to digestive cancers up to June 2020. Two researchers conducted study screening, data extraction, and methodological quality evaluation separately according to inclusion and exclusion criteria. Review Manager 5.3 software was used to conduct the meta-analysis.Results:Six case-control studies were enrolled, including 2477 patients with digestive cancers and 2477 healthy controls. The pooled results showed that the CAV1 rs7804372 (T29107A) polymorphism increased the risk of digestive cancer occurrence in the allele (T vs. A: odds ratio (OR) 1.33, 95% confidence interval (CI): 1.15–1.53, P < .01), homozygous (TT vs. AA: OR 1.72, 95% CI: 1.31–2.26, P < .01), heterozygous (TA vs. AA: OR 1.47, 95% CI: 1.21–1.78, P < .01), dominant (TT vs. TA + AA: OR 1.32, 95% CI: 1.18–1.48, P < .01), and recessive comparing models (TT + TA vs. AA: OR 1.61, 95% CI: 1.26–2.07, P < .01).Conclusion:Our results indicate that the CAV1 (rs7804372) polymorphism may modify the occurrence of digestive cancers, and the presence of T allele or TT genotype of the CAV1 (rs7804372) may increase the risk of digestive cancers.     

Towards an evaluation of alcoholic liver cirrhosis and nonalcoholic fatty liver disease patients with hematological scales

BACKGROUNDSeeking potentially novel blood markers of liver fibrosis and steatosis is constantly of crucial importance. Despite a growing number of studies in this field of hepatology, a certain role of hematological indices in the course of liver disorders has not been fully elucidated, yet.AIMTo evaluate a diagnostic accuracy of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and mean platelet volume-to-platelet-ratio (MPR) in the course of alcoholic liver cirrhosis (ALC) and nonalcoholic fatty liver disease (NAFLD).METHODSOne hundred forty-two patients with ALC, 92 with NAFLD and 68 persons in control group were enrolled in the study. Hematological indices (NLR, PLR and MPR), indirect and direct markers of liver fibrosis (aspartate transaminase to alkaline transaminase ratio, aspartate transaminase to platelet ratio index, fibrosis-4, gamma-glutamyl transpeptidase to platelet ratio, procollagen I carboxyterminal propeptide, procollagen III aminoterminal propeptide, transforming growth factor-α, platelet-derived growth factor AB, laminin) were measured in each person. Model for end-stage liver disease (MELD) score in ALC group and NAFLD fibrosis score together with BARD score were calculated in NAFLD patients. Receiver operating characteristic (ROC) curves and area under the curve (AUC) values were applied to assess the sensitivity and specificity of examined markers and to evaluate proposed cut-offs of measured indices in the course of ALC and NAFLD.RESULTSMPR and NLR values in ALC patients were significantly higher in comparison to control group; PLR level was significantly lower. MPR and PLR correlated with assessed indirect and direct markers of liver fibrosis. MPR, NLR and PLR correlated with MELD score. NLR level in NAFLD patients was significantly higher in comparison to controls. MPR correlated with indirect markers of liver fibrosis and NAFLD fibrosis score. AUC values and proposed cut-offs for NLR, PLR and MPR in ALC patients were: 0.821 (> 2.227), 0.675 (< 70.445) and 0.929 (> 0.048), respectively. AUC values and proposed cut-offs for NLR, PLR and MPR in NAFLD group were: 0.725 (> 2.034), 0.528 (> 97.101) and 0.547 (> 0.038), respectively.CONCLUSIONHematological markers are inseparably connected with serological indices of liver fibrosis in ALC and NAFLD patients. MPR and NLR turned out to be the most powerful parameters in ALC patients.     

Association of TCF7L2 rs7903146 Gene Polymorphism with the Risk of NAFLD and CAD in the Chinese Han Population

Background and Aims: Coronary artery disease (CAD) is a major cause of morbidity and mortality in patients with non-alcoholic fatty liver disease (NAFLD). Previous studies have suggested that TCF7L2 rs7903146 was related to the risk of developing NAFLD but the conclusions are not consistent and no related study has been conducted in Chinese populations. The aim of this study was to investigate the association between TCF7L2 rs7903146 and the risk of developing NAFLD and CAD in a Chinese Han population.Methods: TCF7L2 rs7903146 genotypes were measured by the MALDI-TOF-MS from 143 NAFLD patients, 159 CAD patients, 131 NAFLD + CAD patients, and 212 healthy controls. The demographic data and serum lipid profiles of all subjects were collected. The distributions of genotype and allele frequency in each group were also tested. Logistic regression was used to investigate the risk of TCF7L2 rs7903146 with NAFLD and CAD. All statistical analyses were conducted using SPSS 23.0.Results: There were no significant differences in the distributions of TCF7L2 rs7903146 genotype and allele frequency in each of the two groups, and the TCF7L2 rs7903146 CT + TT genotype did not increase the risk of developing NAFLD, CAD, and NAFLD + CAD. Except for body mass index in the control group, the differences of clinical parameters between the TCF7L2 rs7903146 T allele carriers and non-carriers in each group were not significant. In the non-obese group, the TCF7L2 rs7903146 CT + TT genotype was a protective factor for the development of NAFLD in the non-obese subjects (odds ratio=0.359, 95% confidence interval: 0.134-0.961, p = 0.041).Conclusions: TCF7L2 rs7903146 was not associated with the risk of developing NAFLD, CAD, and NAFLD + CAD in the Chinese Han population. In the non-obese population, the TCF7L2 rs7903146 CT + TT genotype was a protective factor against the development of NAFLD.     

Contribution of a genetic risk score to clinical prediction of hepatic steatosis in obese children and adolescents

BackgroundNonalcoholic fatty liver disease (NAFLD) is the commonest liver disease in children and adolescents in Western countries. Complex traits arise from the interplay between environmental and genetic factors in the pathogenesis of NAFLD.AimsWe examined the association between NAFLD and eleven single nucleotide polymorphisms (SNPs) at genetic loci potentially associated with liver damage (GCKR, MBOAT7, GPR120), oxidative stress (SOD2), lipid metabolism (PNPLA3, TM6SF2, LPIN1, ELOVL2, FADS2, MTTP) and fibrogenesis (KLF6) in a paediatric population. A genetic risk score (GRS) was performed taking into account both these SNPs and clinical risk factors.MethodsWe recruited a cohort of 514 obese children and adolescents (mean age [±SD]: 11.2 ± 2.8 years, z-BMI 3.3 ± 0.8). NAFLD was identified by ultrasonography. Genotyping was performed by TaqMan-based RT-PCR system.ResultsThe overall prevalence of NAFLD was 67.5% (347 patients). Among the eleven genotyped SNPs, the genetic variants in TM6SF2 rs58542926 (OR = 4.13, p = 0.002), GCKR rs1260326 (OR = 1.53, p = 0.003), PNPLA3 rs738409 (OR = 1.58, p = 0.004) and ELOVL2 rs2236212 (OR = 1.34, p = 0.047) were significantly associated with a higher risk of NAFLD. Addition of a 11-polymorphism GRS to established clinical risk factors significantly (albeit modestly) improved the discriminatory capability of the regression model for predicting the risk of NAFLD (with SNPs C-statistic 0.81 [95%CI 0.75–0.88] vs. 0.77 [0.70–0.84] without SNPs; p = 0.047).ConclusionsNAFLD was strongly associated with three genetic variants, TM6SF2 rs58542926, PNPLA3 rs738409 and GCKR rs1260326, and more slightly with ELOVL2 rs2236212, in obese children and adolescents. Addition of a 11-polymorphism GRS to clinical risk factors improved the predictability of NAFLD.