Hepatic lipase (LIPC) C-514T gene polymorphism is associated with cardiometabolic parameters and cardiovascular risk factors but not with fatty liver in Mexican population.

The aim of the present study was to evaluate the role of the C-514T (rs1800588) gene polymorphism of the hepatic lipase (LIPC) as susceptibility marker for fatty liver in the Mexican population. The polymorphism was genotyped by 5' exonuclease TaqMan assays in a group of 1468 subjects (980 with and 488 without fatty liver) belonging to the Genetics of Atherosclerotic Disease (GEA) Mexican Study. Anthropometric and biochemical measurements were performed on all individuals. The polymorphism was not associated with fatty liver, however, under dominant model, the TT genotype was associated with increased levels of triglycerides (P=0.0002), apolipoprotein A1 (P=0.015), triglycerides/HDL-cholesterol index (P=0.046) and increased frequency of type 2 diabetes mellitus (P=0.045). On the other hand, the same genotype was associated with the presence of small LDLs (P=0.003). The risk analysis showed that under a dominant model, the LIPC C-514T polymorphism was associated with increased risk of type 2 diabetes (OR=1.42, P=0.029), hypertriglyceridemia (OR=1.36, P=0.006), and coronary artery calcification (CAC)≥1 (OR=1.44, P=0.015) and decreased risk of hypoalphalipoproteinemia (OR=0.78, P=0.036). The results suggest that the LIPC C-154T polymorphism is associated with cardiometabolic parameters and cardiovascular risk factors but not with fatty liver in Mexican population. The association detected with CAC indicates that this polymorphism could be a marker for subclinical atherosclerosis.

Olive oil increases the LIPC expression when associated with an Eastern pattern diet: An experimental study with Wistar rats.

Some nutrigenomic effects of extra virgin olive oil (EVOO) are described in the literature; however, it is unknown whether its interaction with lipid-related genes is independent of the combined diet. In this sense, our objective was to investigate whether EVOO consumption associated with Western or Eastern human-based chow modulates the expression of APOE, APOB, and LIPC genes in rats. In view of this, the hypothesis is that the consumption of olive oil may not have the same nutrigenomic effects, depending on the diet consumed. For this study, 56 female rats were randomly divided into four groups: Western diet with EVOO (WS), Western-diet control (WC), Eastern-diet with EVOO (ES), and Eastern-diet control (EC). After 15 weeks, the animals were anesthetized with an intraperitoneal injection of chloral hydrate 15% (1.5 mL/kg) and euthanized by guillotining, and adipose tissue, liver, and blood were extracted. Triglycerides, cholesterol, and glucose levels were obtained following standard protocols, and relative gene expressions were calculated using the ΔΔCt method after quantitative PCR. The EVOO consumption was associated with LIPC gene expression increase in the liver only in animals fed the Eastern diet, compared to EC and WS animals. The EVOO consumption, combined with the Eastern diet, was associated with decreased triglyceride levels compared to WC. Although final weight and weight gain were similar between groups, WS animals had lower daily energy consumption. Conclusion: Given these results, the authors suggested that the EVOO nutrigenomic effects were restricted to an Eastern human-based diet.

Hypertriglyceridemia Induced Acute Pancreatitis Caused by a Novel LIPC Gene Variant in a Pediatric Patient.

Hypertriglyceridemia induced acute pancreatitis is a rare cause of pancreatitis in children. Hepatic lipase deficiency is an extremely rare cause of hypertriglyceridemia, reported in only a few families to date. Hepatic lipase is the enzyme involved in the hydrolysis of triglycerides and phospholipids in remnants of triglyceride-rich lipoproteins that have a role in the conversion of very low density lipoprotein remnants to low density lipoproteins. Hepatic lipase deficiency is inherited in an autosomal recessive pattern. Detection of heterozygous carriers of hepatic lipase mutations remains accidental at the population level, as affected persons with a heterozygous state of hepatic lipase mutation do not display specific lipoprotein abnormalities and also patients with complete hepatic lipase deficiency have inconstant phenotype. The proximal promoter of the LIPC gene consists of four polymorphic sites in complete linkage disequilibrium. Five missense mutations in encoding exons have been described and proved to be responsible for hepatic lipase deficiency to date: S267F, T383M, L334F, A174T, and R186H, affecting the activity and secretion of hepatic lipase. We identified a primary disorder of the lipid metabolism as the cause of the acute episode of pancreatitis in a four years old patient, consisting of hepatic lipase deficiency caused by a novel genetic variant of the LIPC gene, a gross deletion of the genomic region encompassing exon 1. This variant was not previously described in the literature in persons with LIPC-related disorders and its significance is currently uncertain, but in the presented clinical and paraclinical context, it has the characteristics of a pathological variant inducing a hepatic lipase deficiency phenotype.

Association between two common polymorphisms (single nucleotide polymorphism -250G/A and -514C/T) of the hepatic lipase gene and coronary artery disease in type 2 diabetic patients.

BACKGROUND: Variations in the hepatic lipase (HL) gene are the potential candidate for coronary artery disease (CAD) especially in type 2 diabetes mellitus (T2DM) in diverse populations. We assessed the association of -514C/T and -250G/A polymorphisms in HL (LIPC) gene with CAD risk in Iranian population with type 2 diabetes. MATERIALS AND METHODS: We evaluated 322 type 2 diabetic patients, 166 patients with normal angiograms as controls and 156 patients those identified with CAD undergoing their first coronary angiography as CAD cases. Genotyping of -514C/T and -250G/A polymorphisms in the promoter of the LIPC gene were studied by polymerase chain reaction (PCR)-restriction fragment length polymorphism technique. RESULTS: Genotype distributions in CAD cases (73.7%, 20.5%, and 5.8% for -250G/A) and (62.2%, 32.7%, and 5.1% for -514C/T) were significantly different from those in controls (60.8%, 37.4%, and 1.8% for -250G/A) and (51.2%, 48.2%, and 0.6% for -514C/T). CAD cases had lower A-allele frequency than controls (0.131 vs. 0.196, P = 0.028). The odds ratio for the presence of -250 (GG + GA) genotype and A allele in CAD cases were 2.206 (95% confidence interval [CI] =1.33-3.65, P = 0.002) and 1.609 (95% CI = 1.051 -2.463, P = 0.029) respectively. Haplotype analysis demonstrated a significant association between especially LIPC double mutant (-250 A/-514 T) haplotype and presence of CAD. CONCLUSION: Our findings indicated that -250 G/A polymorphism rather than -514 C/T polymorphism of LIPC gene is more associated with the increased risk of CAD particularly in women with T2DM.

The rs2070895 (-250G/A) Single Nucleotide Polymorphism in Hepatic Lipase (HL) Gene and the Risk of Coronary Artery Disease in North Indian Population: A Case-Control Study.

INTRODUCTION: Several Single Nucleotide Polymorphisms (SNPs) in lipid transport genes have been shown to be associated with Coronary Artery Disease (CAD). The Hepatic Lipase (HL)glycoprotein is a key component that catalyzes the hydrolysis of triglycerides and phospholipids in all major classes of lipoproteins. AIM: We studied whether the HL gene-250G/A polymorphism affect blood lipid level and the CAD in a North Indian population. MATERIALS AND METHODS: A total number of 477 subjects were enrolled in the study after approval of the Institutional Ethics Committee. Out of 477 subjects, 233 were with coronary artery disease as study group and 244 subjects without coronary artery disease as control group. All subjects recruited with matched ethnicity in age group of 40-70 years. Blood samples were collected in EDTA vials and genomic DNA was extracted from blood using the phenol-chloroform method. Lipid profile was estimated by using a commercially available kit. Polymorphisms in the HL (-250 G/A) gene were analysed by using restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP) method. The effect of this polymorphism on plasma lipids, lipoproteins and coronary artery disease was determined. RESULTS: In Human Hepatic Lipase (LIPC)-250G/A genotype, the frequencies of GG, GA and AA genotype in CAD group was 80.69%, 15.45% and 3.86%, respectively; in the control group, the corresponding frequencies were 90.16%, 9.02% and 0.82%, respectively. A significant difference was found in the genotype (LIPC-250G/A) distribution between the two groups. Further logistic regression analysis indicated that the GA and AA genotypes in SNP-250G/A were significantly associated with CAD in all genetic models (In codominant model- GA vs. GG, OR=1.91, 95% CI=1. 09-3.37, p=0. 03 and AA vs. GG, OR= 5.26, 95% CI= 1.10-24.60, p=0.04; in dominant model- GA+AA vs. GG, OR=2.19, p=0.004 and in recessive model- AA vs. GG+GA, OR=5.26, p=0.04 whereas, A allele at nucleotide -250G/A in the LIPC gene had an association with increased risk of CAD (OR=2.33, p=<0.008). CONCLUSION: Our findings indicated that the higher frequency of a dominant model (GA+AA) as well as mutant allele A of LIPC-250 G/A polymorphism is significantly associated with risk of CAD and the lipid profile can be used as a predictor of CAD.