Associations of systemic, serum lipid and lipoprotein metabolic pathway gene variations with polypoidal choroidal vasculopathy in China

Abstract

BackgroundTo investigate the association of systemic, serum lipids and genetic variants in the high-density lipoprotein (HDL) metabolic pathway with polypoidal choroidal vasculopathy (PCV) in China.MethodsThe case-control study was included 150 controls and 66 cases with PCV. Serum levels of total cholesterol (TC), low-density lipoprotein (LDL), HDL, triglycerides (TG), apolipoprotein A1 (APOA1), apolipoprotein B (APOB) together with systemic risk factors including gender, hyperlipidemia, diabetes mellitus (DM), hypertension, coronary artery disease (CAD) and asthma were identified. All subjects were genotyped for four single nucleotide polymorphisms (SNPs) from three genes in the HDL metabolic pathway: rs10468017 of hepatic lipase (LIPC), rs12678919 of lipoprotein lipase (LPL), rs3764261 and rs173539 of cholesterol ester transfer protein (CETP) with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Student’s t-tests, chi-square tests, anova and logistic regression were used to evaluate associations.ResultsHyperlipidemia was a risk factor (odds ratio (OR) = 1.19, P = 0.001) for PCV. HDL, LDL and APOB levels were associated with PCV (OR = 0.001, P = 0.004; OR = 0.099, P = 0.010; OR = 0.839, P = 0.018). Higher level of TC was potently associated with increased risk of PCV (OR = 109.8, P = 0.000). LIPC rs10468017 was a risk factor for PCV (OR = 11.68, P = 0.000). CETP rs3764261 conferred a decreased risk for PCV (OR = 0.08, P = 0.000). No associations of LPL rs12678919 or CETP rs173539 with PCV were found. Mean level of HDL increased with T allele of the CETP gene (p = 0.026): 1.24 mmol/L (±0.31) for the GG genotype and 1.66 mmol/L (±0.54) for the TT genotype. Additionally, T allele was associated with the following increase in APOA1: 136.78 mg/dl (±20.53) for the CC genotype and 149.57 mg/dl (±22.67) for the TT genotype of LIPC and 137.91 mg/dl (±20.36) for the GG genotype and 162.67 mg/dl (±22.50) for the TT genotype of CETP gene.ConclusionOur study suggested that the significant association was found between hyperlipidemia, the serum levels of TC, HDL, LDL and APOB and PCV. The result of present study also showed that the association of LIPC rs10468017 and CETP rs3764261 with PCV.

The Underlying Mechanisms of Curcumin Inhibition of Hyperglycemia and Hyperlipidemia in Rats Fed a High-Fat Diet Combined With STZ Treatment

“…These findings are similar to the result of previous in vitro experiment, in which curcumin decreased glycerol release in differentiated 3T3-L1 adipocytes, as it has a certain effect on regulating lipid metabolism dysfunction [40]. Generally, HDL-C could stimulate cell growth and tissue regeneration, and is helpful for the prevention of oxidant stress-disease including atherosclerosis and coronary heart disease [41,42]. However, in our study, HF + STZ treatment resulted in the highest blood HDL-C level in rats.…”

Association of genetic variants at CETP, AGER, and CYP4F2 locus with the risk of atrophic age‐related macular degeneration

“…CETP rs708272 was shown to be associated with total cholesterol level changes (Iwanicka et al, 2018), with the risk of coronary atherosclerosis (Wang et al, 2013) and myocardial infarction (Semaev et al., 2019), which are linked to AMD as well (Liutkeviciene et al., 2012). CETP rs3764261 was also associated with serum HDL and APOA1 levels (Huang et al, 2019; Xu, 2019). Moreover, controversial results were found in AMD analysis, the minor allele at CETP rs3764261 was proved to be a risk factor to the development of AMD (Cheng, 2015), while in the other study it played the protective role (Wang, Zhou, et al, 2015).…”

Differentially Regulated Apolipoproteins and Lipid Profiles as Novel Biomarkers for Polypoidal Choroidal Vasculopathy and Neovascular Age-Related Macular Degeneration

“…Lipoproteins are soluble lipid protein complexes that are formed by the interactions between apolipoproteins (apos, amphipathic proteins) and lipids (10). Abnormal expression of genes of lipid metabolism and the reverse cholesterol transport (RCT) pathway, such as Cholesterol Ester Transfer Protein (CETP), Hepatic Lipase (LIPC), ATP-binding Cassette Transporter A1 (ABCA1) and Apolipoprotein E (APOE), has been reported in patients with PCV and nAMD (11)(12)(13). Furthermore, dysregulated lipoproteins [triglycerides (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein (LDL-C)] and apolipoproteins have been reported in both PCV and nAMD (12,14,15); however, results from existing studies are controversial and the connections remain elusive (15,16).…”