High-Density Lipoprotein Cholesterol in Age-Related Ocular Diseases

Betzler, Bjorn Kaijun; Rim, Tyler Hyungtaek; Sabanayagam, Charumathi; Cheung, Chui Ming Gemmy; Cheng, Ching‐Yu

doi:10.3390/biom10040645

Cited by 21 publications

(15 citation statements)

References 142 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, several studies have shown that age-related macular degeneration, a leading cause of irreversible vision loss, is positively associated with HDL-C, although conflicting results have remained. [26][27][28] A forest plot in the meta-analysis by Wang et al 26 showed a significant association between HDL-C and age-related macular degeneration, suggesting that people with high HDL-C levels may be at increased risk for age-related macular degeneration.…”

Section: Discussionmentioning

confidence: 99%

Association between extremely high high-density lipoprotein-cholesterol and hypertensive retinopathy: results of a cross-sectional study from Kanagawa Investigation of Total Checkup Data from the National Database-6 (KITCHEN-6)

et al. 2021

View full text Add to dashboard Cite

ObjectivesDoubt has been cast on the atheroprotective effect of very high high-density lipoprotein cholesterol (HDL-C). Hypertensive retinopathy (HR) is caused by persistent systemic hypertension. Therefore, we aimed to investigate the association between extremely high HDL-C (EH-HDL) and HR.DesignA cross-sectional study.ParticipantsA total of 4072 general Japanese population aged 40–74 years who underwent regular medical check-ups including fundus examinations.Outcome measuresHR and clinical parameters including serum HDL-C were investigated. HR was determined by the Keith-Wagener classification and the Scheie classifications for Hypertension and Atherosclerosis (n=4054 available). Serum HDL-C was divided into five categories: 30–49, 50–69, 70–89, 90–109 and ≥110 mg/dL.ResultsOverall, 828 (20.3%) subjects had Keith-Wagener-HR, 578 (14.3%) had hypertension-HR, and 628 (15.5%) had atherosclerosis-HR. Blood pressure decreased as HDL-C level increased, whereas the prevalences of HRs showed U-shaped curves against HDL-C with minimum values for HDL-C 90–109 mg/dL. In logistic regression analyses, EH-HDL ≥110 mg/dL was significantly associated with Keith-Wagener-HR and atherosclerosis-HR, compared with HDL-C 90–109 mg/dL after adjustments for age, sex and systolic blood pressure (OR 3.01, 95% CI 1.45 to 6.27 and OR 2.23, 95% CI 1.03 to 4.86). The hypertension-HR was not significantly associated with EH-HDL regardless of adjustment for the confounding factors (p=0.05–0.08). Although serum HDL-C as a continuous variable was inversely associated with three HRs, which disappeared after adjustment for the confounding factors.ConclusionEH-HDL may be associated with HR independently of blood pressure, suggesting that EH-HDL reflects a special atherosclerotic condition.

show abstract

Section: Discussionmentioning

confidence: 99%

Association between extremely high high-density lipoprotein-cholesterol and hypertensive retinopathy: results of a cross-sectional study from Kanagawa Investigation of Total Checkup Data from the National Database-6 (KITCHEN-6)

et al. 2021

View full text Add to dashboard Cite

show abstract

“…MIR4453HG is an IncRNA gene and located nearby some risk genes that have been reported to be associated with blood protein level (gene ARFIP1 48 ) and lipoprotein cholesterol levels (gene TRIM2 49 ). Both traits are highly relevant to the risk for type 2 diabetes 50,51 and cataract 52,53 . KCNK17 encoded a protein in the family of potassium channel 54 .…”

Section: Discussionmentioning

confidence: 99%

The putative causal effect of type 2 diabetes in risk of cataract: a Mendelian randomization study in East Asian

Zhang

Xue

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: The epidemiological association between type 2 diabetes and cataract has been well-established. However, it remains unclear whether the two diseases share a genetic basis, and if so, whether this reflects a causal relationship. Methods: We utilized East Asian population-based genome-wide association studies (GWAS) summary statistics of type 2 diabetes (Ncase=36,614, Ncontrol=155,150) and cataract (Ncase=24,622, Ncontrol=187,831) to comprehensively investigate the shared genetics between the two diseases. We performed 1. linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics (ρ-HESS) to estimate the genetic correlation and local genetic correlation between type 2 diabetes and cataract; 2. multiple Mendelian randomization (MR) analyses to infer the putative causality between type 2 diabetes and cataract; and 3. Summary-data-based Mendelian randomization (SMR) to identify candidate risk genes underling the causality. Results: We observed a strong genetic correlation (rg=0.58; p-value=5.60 times 10^-6) between type 2 diabetes and cataract. Both rho-HESS and multiple MR methods consistently showed a putative causal effect of type 2 diabetes on cataract, with estimated liability-scale MR odds ratios (ORs) at around 1.10 (95% confidence interval [CI] ranging from 1.06 to 1.17). In contrast, no evidence supports a causal effect of cataract on type 2 diabetes. SMR analysis identified two novel genes MIR4453HG (beta for SMR=-0.34, p-value=6.41 times 10^-8) and KCNK17 (beta for SMR=-0.07, p-value=2.49 times 10^-10), whose expression levels were likely involved in the putative causality of type 2 diabetes on cataract. Conclusions: Our results provided robust evidence supporting a causal effect of type 2 diabetes on the risk of cataract in East Asians, and posed new paths on guiding prevention and early-stage diagnosis of cataract in type 2 diabetes patients.

show abstract

“…Tangier disease (OMIM# 205400) is caused by recessive mutations in ABCA1, and is characterized by hypoalphalipoproteinemia (low serum ApoA1-HDL levels), mild neuropathy, atherosclerosis, retinopathy, corneal infiltrates and scarring, lipid deposits in the conjunctiva, and cataract formation (29). [The reader is referred to a recent review that provides detailed analysis of the specific role of HDL in age-related retinopathies (30).] This review discusses the role of sterol efflux in retinal physiology and pathophysiology.…”

Section: General Considerations: Cholesterol Synthesis Uptake and Ementioning

confidence: 99%

Cholesterol homeostasis in the vertebrate retina: biology and pathobiology

Rao

Fliesler

2021

Journal of Lipid Research

View full text Add to dashboard Cite

Cholesterol is a quantitatively and biologically significant constituent of all mammalian cell membrane, including those that comprise the retina. Retinal cholesterol homeostasis entails the interplay between de novo synthesis, uptake, intra-retinal sterol transport, metabolism and efflux. Defects in these complex processes are associated with several congenital and age-related disorders of the visual system. Herein, we provide an overview of the following topics: a) cholesterol synthesis in the neural retina; b) lipoprotein uptake and intraretinal sterol transport in the neural retina and the retinal pigment epithelium (RPE); c) cholesterol efflux from the neural retina and the RPE; and d) biology and pathobiology of defects in sterol synthesis and sterol oxidation in the neural retina and the RPE. We focus, in particular, on studies involving animal models of monogenic disorders pertinent to the above topics, as well as in vitro models using biochemical, metabolic, and omic approaches. We also identify current knowledge gaps as well as opportunities in the field that beg further research in this topic area.

show abstract

High-Density Lipoprotein Cholesterol in Age-Related Ocular Diseases

Cited by 21 publications

References 142 publications

Association between extremely high high-density lipoprotein-cholesterol and hypertensive retinopathy: results of a cross-sectional study from Kanagawa Investigation of Total Checkup Data from the National Database-6 (KITCHEN-6)

Association between extremely high high-density lipoprotein-cholesterol and hypertensive retinopathy: results of a cross-sectional study from Kanagawa Investigation of Total Checkup Data from the National Database-6 (KITCHEN-6)

The putative causal effect of type 2 diabetes in risk of cataract: a Mendelian randomization study in East Asian

Cholesterol homeostasis in the vertebrate retina: biology and pathobiology

Contact Info

Product

Resources

About