Associations of systemic, serum lipid and lipoprotein metabolic pathway gene variations with polypoidal choroidal
Ningda Xu1, Hui Xu1, Mingwei Zhao1
1Department of Ophthalmology, Peking University People's Hospital Eye Diseases and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, College of Optometry, Peking University Health Science Center; Beijing,China.
Insights
This study found hyperlipidemia and specific serum lipid levels (total cholesterol, HDL, LDL, APOB) are associated with polypoidal choroidal vasculopathy (PCV). Genetic variants in LIPC and CETP genes also showed significant links to PCV risk.
Area of Science:
- Ophthalmology
- Genetics
- Cardiovascular Research
Background:
- Polypoidal choroidal vasculopathy (PCV) is a significant cause of vision impairment.
- Understanding the role of systemic factors and genetic predispositions is crucial for PCV research.
- The high-density lipoprotein (HDL) metabolic pathway is implicated in various vascular conditions.
Purpose of the Study:
- To investigate the association between serum lipid profiles, genetic variants in the HDL pathway, and PCV in a Chinese population.
- To identify potential biomarkers for PCV risk assessment.
Main Methods:
- A case-control study involving 66 PCV cases and 150 controls.
- Analysis of serum lipid levels (TC, LDL, HDL, TG, APOA1, APOB) and systemic risk factors.
- Genotyping of four single nucleotide polymorphisms (SNPs) in LIPC, LPL, and CETP genes using MALDI-TOF-MS.
- Statistical analysis including t-tests, chi-square tests, ANOVA, and logistic regression.
Main Results:
- Hyperlipidemia was identified as a risk factor for PCV (OR = 1.19, P = 0.001).
- Serum levels of TC, HDL, LDL, and APOB were significantly associated with PCV.
- The LIPC rs10468017 SNP was a risk factor (OR = 11.68, P = 0.000), while CETP rs3764261 showed a decreased risk (OR = 0.08, P = 0.000).
- Specific genotypes of CETP and LIPC correlated with altered HDL and APOA1 levels.
Conclusions:
- Systemic hyperlipidemia and specific serum lipid levels are significantly associated with PCV.
- Genetic variants in LIPC (rs10468017) and CETP (rs3764261) are linked to PCV risk.
- These findings highlight the interplay of metabolic and genetic factors in the pathogenesis of PCV.
Background:
To 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.
Methods:
The 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.
Results:
Hyperlipidemia 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.
Conclusion:
Our 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.
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