0
selected
-
1.
The rs738409 G Allele in PNPLA3 Is Associated With a Reduced Risk of COVID-19 Mortality and Hospitalization.
Innes, H, Buch, S, Barnes, E, Hampe, J, Marjot, T, Stickel, F
Gastroenterology. 2021;(7):2599-2601.e2
-
2.
PNPLA3 Gene Polymorphism Is Associated With Predisposition to and Severity of Alcoholic Liver Disease.
Salameh, H, Raff, E, Erwin, A, Seth, D, Nischalke, HD, Falleti, E, Burza, MA, Leathert, J, Romeo, S, Molinaro, A, et al
The American journal of gastroenterology. 2015;(6):846-56
-
-
Free full text
-
Abstract
OBJECTIVES The genetic polymorphism with an isoleucine-to-methionine substitution at position 148 (rs738409 C>G) in the patatin-like phospholipase domain protein 3 (PNPLA3) gene confers risk of steatosis. PNPLA3 polymorphism is shown to be associated with alcoholic liver disease (ALD). We performed a systematic review and meta-analysis to examine association of this genetic polymorphism with ALD spectrum and its severity. METHODS Medline, Embase, and Cochrane Library were searched for studies on association of PNPLA3 polymorphism and ALD spectrum: alcoholic fatty liver (AFL), alcoholic liver injury (ALI), alcoholic cirrhosis (AC), and hepatocellular carcinoma (HCC). Pooled data are reported as odds ratio (OR) with 95% confidence interval. Heterogeneity was assessed using the I(2) statistics and publication bias using Egger's test and Begg and Mazumdar's test. Individual participant data obtained from five studies were used for subgroup analyses. RESULTS Among 10 studies included in this pooled analysis, compared with controls, OR for rs738409 CG and GG among ALI patients was 1.45 (1.24-1.69) and 2.22 (1.50-3.28), respectively, compared with CC. Respective OR among AC patients was 2.09 (1.79-2.44) and 3.37 (2.49-4.58) and among AC patients with HCC was 2.87 (1.61-5.10) and 12.41 (6.99-22.03). Data for AFL were inconsistent. Among ALD patients, OR of CG and GG genotypes was 2.62 (1.73-3.97) and 8.45 (2.52-28.37), respectively, for AC compared with fatty liver (FL) patients. Similar OR for AC compared with ALI was 1.98 (1.24-3.17) and 3.86 (1.18-12.60). The OR for CG and GG genotypes among AC patients for HCC occurrence was 1.43 (0.76-2.72) and 2.81 (1.57-5.01), respectively. Individual participant data analysis showed age to predispose to AC among ALI patients. CONCLUSIONS PNPLA3 genetic polymorphism (rs738409 C>G) is associated with increased risk for the entire spectrum of ALD among drinkers including ALI, AC, and HCC. Studies are needed to clarify association of PNPLA3 polymorphism and steatosis in alcoholics. PNPLA3 gene may potentially be a therapeutic target in ALD.
-
3.
Gender specific effect of LIPC C-514T polymorphism on obesity and relationship with plasma lipid levels in Chinese children.
Wang, H, Zhang, D, Ling, J, Lu, W, Zhang, S, Zhu, Y, Lai, M
Journal of cellular and molecular medicine. 2015;(9):2296-306
-
-
Free full text
-
Abstract
Hepatic lipase (LIPC) is a key rate-limiting enzyme in lipoprotein catabolism pathways involved in the development of obesity. The C-514T polymorphism in the promoter region is associated with decreased LIPC activity. We performed a case-controlled study (850 obese children and 2119 controls) and evaluated the association between LIPC C-514T polymorphism, obesity and plasma lipid profile in Chinese children and adolescents. Additionally, we conducted a meta-analysis of all results from published studies as well as our own data. A significant association between the polymorphism and obesity is observed in boys (P = 0.042), but not in girls. And we observed a significant relationship of the polymorphism with total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) independent of obesity in boys. The T allele carriers have higher levels of low density lipoprotein cholesterol (LDL-C) in obese boys, and triglyceride (TG), TC and LDL-C in non-obese girls (all P < 0.05). In the meta-analysis, under dominant model the T allele increased body mass index (BMI) level in boys, while it decreased BMI in girls, and increased the levels of TC both in the overall and subgroups, TG and HDL-C in the overall and boys, and LDL-C in the overall (all P < 0.05). Our results suggest that the T allele might carry an increased risk of obesity in Chinese boys. The meta-analysis suggests that T allele acts as a risk allele for higher BMI levels in male childhood, while it is a protective allele in female childhood. And the polymorphism is associated with the levels of plasma lipids, which may be modulated by obesity and gender.
-
4.
CETP/LPL/LIPC gene polymorphisms and susceptibility to age-related macular degeneration.
Wang, YF, Han, Y, Zhang, R, Qin, L, Wang, MX, Ma, L
Scientific reports. 2015;:15711
Abstract
Three high-density lipoprotein (HDL)-related loci have been reported to be associated with age-related macular degeneration (AMD), but the results were inconsistent. In this study, the cholesteryl ester transfer protein (CETP) rs3764261 variant was significantly associated with an increased risk of AMD (odds ratio [OR] = 1.13, 95% confidence interval [CI]: 1.05-1.21, P < 0.001), and the hepatic lipase (LIPC) rs10468017 variant was associated with a significantly decreased risk of AMD (OR = 0.81, CI: 0.76-0.86, P < 0.001). Individuals carrying the lipoprotein lipase (LPL) rs12678919 polymorphism (A → G) had no significant change in the risk of developing AMD (OR = 1.01, CI: 0.92-1.10, P = 0.17). After adjusting for the complement factor H (CFH) gene, both CETP and LPL conferred a significantly increased AMD risk (ORCETP = 1.17, CI: 1.08-1.26, P < 0.001; ORLPL = 1.11, CI: 1.01-1.22, P = 0.02). Subgroup analysis based on ethnicity revealed a significant association between the CETP variant and AMD in both Americans (OR = 1.12, CI: 1.02-1.23, P = 0.01) and Europeans (OR = 1.10, CI: 1.01-1.19, P = 0.011). This meta-analysis revealed that both CETP rs3764261 and LIPC rs10468017 polymorphisms were significantly associated with AMD risk. After adjustment for the CFH gene, CETP/LPL conferred a significantly increased susceptibility to the disease, indicating potential interactions among genes in the complement system and the lipid metabolism pathway.
-
5.
The associations between endothelial lipase 584C/T polymorphism and HDL-C level and coronary heart disease susceptibility: a meta-analysis.
Cai, G, Huang, Z, Zhang, B, Weng, W, Shi, G
Lipids in health and disease. 2014;:85
Abstract
BACKGROUND Studies had investigated the relationships between endothelial lipase (EL) 584C/T polymorphism and high density lipoprotein cholesterol (HDL-C) level and coronary heart disease (CHD), but the results were controversial. To investigate a more authentic associations between EL 584C/T polymorphism and HDL-C level, and the risk of CHD, we performed this meta-analysis. METHODS We searched electric databases for all articles on the associations between EL 584C/T polymorphism and HDL-C level, and CHD risk. Odds ratios (ORs) with 95% confidence interval (CI) were used to evaluate the strength of the association between the EL 584C/T polymorphism and the CHD susceptibility. The pooled standardized mean difference (SMD) with 95% CI was used for the meta-analysis of EL 584C/T polymorphism and HDL-C level. Begg's funnel plots and Egger's test were used to examine the publication bias. RESULTS For CHD association, the pooled OR was 0.829 (95% CI: 0.701-0.980, P = 0.028) for the dominant model and 0.882 (95% CI: 0.779-0.999, P = 0.049) for the allelic model. By meta-regression analysis, we found that only total sample size could influence the initial heterogeneity. When the subgroup analysis was carried out, we found that the protective effect only existed in the subgroups of relatively small sample size. Sensitivity analyses indicated that Tang's study influenced the overall results significantly. We calculated the pooled ORs again after excluding Tang's study and found the association between EL 584C/T polymorphism and the risk of CHD was not significant for any genetic model. For HDL-C level association, the carriers of 584 T allele had a higher HDL-C level than the non-carriers. The pooled SMD was 0.399 (95% CI: 0.094-0.704, P = 0.010). When the studies were stratified by ethnicity and total sample size, the positive effects existed in the Caucasians and in subgroups of larger sample size. No significant publication bias was found in the present meta-analysis. CONCLUSIONS The results of the present meta-analysis suggest that the carriers of EL 584 T allele have a higher HDL-C level in Caucasian populations. Whereas, it might not be a protective factor for CHD.
-
6.
The PNPLA3 rs738409 G-allele associates with reduced fasting serum triglyceride and serum cholesterol in Danes with impaired glucose regulation.
Krarup, NT, Grarup, N, Banasik, K, Friedrichsen, M, Færch, K, Sandholt, CH, Jørgensen, T, Poulsen, P, Witte, DR, Vaag, A, et al
PloS one. 2012;(7):e40376
Abstract
BACKGROUND AND AIM Non-alcoholic fatty liver disease (NAFLD) is a common condition, associated with hepatic insulin resistance and the metabolic syndrome including hyperglycaemia and dyslipidemia. We aimed at studying the potential impact of the NAFLD-associated PNPLA3 rs738409 G-allele on NAFLD-related metabolic traits in hyperglycaemic individuals. METHODS The rs738409 variant was genotyped in the population-based Inter99 cohort examined by an oral glucose-tolerance test, and a combined study-sample consisting of 192 twins (96 twin pairs) and a sub-set of the Inter99 population (n = 63) examined by a hyperinsulinemic euglycemic clamp (n(total) = 255). In Inter99, we analyzed associations of rs738409 with components of the WHO-defined metabolic syndrome (n = 5,847) and traits related to metabolic disease (n = 5,663). In the combined study sample we elucidated whether the rs738409 G-allele altered hepatic or peripheral insulin sensitivity. Study populations were divided into individuals with normal glucose-tolerance (NGT) and with impaired glucose regulation (IGR). RESULTS The case-control study showed no associations with components of the metabolic syndrome or the metabolic syndrome. Among 1,357 IGR individuals, the rs738409 G-allele associated with decreased fasting serum triglyceride levels (per allele effect(β) = -9.9% [-14.4%;-4.0% (95% CI)], p = 5.1×10(-5)) and fasting total cholesterol (β = -0.2 mmol/l [-0.3;-0.01 mmol/l(95% CI)], p = 1.5×10(-4)). Meta-analyses showed no impact on hepatic or peripheral insulin resistance in carriers of the rs738409 G-allele. CONCLUSION Our findings suggest that the G-allele of PNPLA3 rs738409 associates with reduced fasting levels of cholesterol and triglyceride in individuals with IGR.
-
7.
The -514 C->T hepatic lipase promoter region polymorphism and plasma lipids: a meta-analysis.
Isaacs, A, Sayed-Tabatabaei, FA, Njajou, OT, Witteman, JC, van Duijn, CM
The Journal of clinical endocrinology and metabolism. 2004;(8):3858-63
Abstract
Investigations of the -514 C-->T single nucleotide polymorphism (SNP) in the hepatic lipase (HL) gene promoter region (LIPC) have yielded contradictory results regarding its association with changes in plasma lipids. The current study is a meta-analysis of 25 publications on this SNP, comprising over 24,000 individuals, and its relationship with total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL), triglycerides, and HL activity. Significant decreases were observed in HL activity for both the CT and TT genotypes compared with the CC genotype [weighted mean difference (WMD), -5.83 mmol/liter.h (95% confidence interval, -8.48, -3.17) and -11.05 mmol/liter.h (95% confidence interval, -14.74, -7.36), respectively]. Moreover, significant increases in HDL were found; the CT to CC comparison showed an increase in WMD of 0.04 mmol/liter (95% confidence interval, 0.02, 0.05) mmol/liter, and the increase in the TT vs. CC difference was WMD of 0.09 mmol/liter (95% confidence interval, 0.07, 0.12). These changes appear to be stepwise, implying an allele dosage effect. All P values for these associations were less than 0.001. This meta-analysis demonstrates the importance of the -514C-->T SNP in determining HL activity and plasma HDL concentration and helps quantify the role that hepatic lipase plays in the metabolism of HDL.