Phenotype in Individuals with Heterozygous Rare Variants in LIPC Encoding Hepatic Lipase

Figures

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  Figure 1. Lipid and lipoprotein levels of patients with LIPC variants compared to population controls. The plasma levels of total cholesterol (TC) (A), low-density lipoprotein cholesterol (LDL-C) (B), high-density lipoprotein cholesterol (HDL-C) (C), and triglycerides (TG) (D) were measured in patients with LIPC variants. Each patient’s levels were converted to percentile values, with the average percentile of the cohort displayed above (vertical line). The reference percentile values were obtained from the LRC prevalence study (North America). The distributions were formed using data from 50–55-year-old women, corresponding to the average age and sex of the cohort.

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  Figure 2. Lipid levels of patients with LIPC variants compared to normal controls. Plasma levels of total cholesterol (TC) (green), low-density lipoprotein cholesterol (LDL-C) (purple), high-density lipoprotein cholesterol (HDL-C) (orange), triglycerides (log(TG)) (blue), and apolipoprotein (apo) B (pink) were compared between patients with LIPC variants (n = 46) and normal controls (n = 72). The darker color corresponds to the LIPC cohort, the lighter to the control. Unpaired one-tailed t-tests were used to compare the lipid levels between cohorts: ‘*’ denotes a p-value < 0.05 and ‘**’ denotes a p-value < 0.0001. The one-tailed p-value between LIPC and control groups is 1.5 × 10−6 for TC, 0.019 for LDL-C, 0.11 for HDL-C, 5.4 × 10−9 for log(TG), and 0.20 for Apo B.

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  Figure 3. Lipid levels of patients with pathogenic LIPC variants compared to normal controls. Plasma levels of total cholesterol (TC) (green), low-density lipoprotein cholesterol (LDL-C) (purple), high-density lipoprotein cholesterol (HDL-C) (orange), triglycerides (log(TG)) (blue), and apolipoprotein B (Apo B) (pink) were compared among patients with pathogenic or likely pathogenic LIPC variants (n = 13) and normal controls (n = 72). The darker color corresponds to the LIPC cohort, the lighter to the control. Unpaired one-tailed t-tests were used to compare the lipid levels between cohorts, ‘*’ denotes a p-value < 0.05 and ‘**’ denotes a p-value < 0.0001: TC p = 5.7 × 10−5, LDL-C p = 0.011, HDL-C p = 0.039, log(TG) p = 5.9 × 10−3, and Apo B p = 0.005.

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  Figure 4. Lipid levels of patients with benign LIPC variants compared to normal controls. Plasma levels of total cholesterol (TC) (green), low-density lipoprotein cholesterol (LDL-C) (purple), high-density lipoprotein cholesterol (HDL-C) (orange), triglycerides (log(TG)) (blue), and apolipoprotein B (Apo B) (pink) were compared among patients with benign or likely benign LIPC variants (n = 4) and normal controls (n = 72). The darker color corresponds to the LIPC cohort, the lighter to the control. Unpaired one-tailed t-tests were used to compare the lipid levels between cohorts, ‘*’ denotes a p-value < 0.05. The one-tailed p-value between the LIPC group and the control group is 0.159 for TC, 0.313 for LDL-C, 0.385 for HDL-C, 0.048 for log(TG), and 0.25 for Apo B.

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  Figure 5. Lipid levels of patients with AI-predicted pathogenic LIPC variants compared to normal controls. Plasma levels of total cholesterol (TC) (green), low-density lipoprotein cholesterol (LDL-C) (purple), high-density lipoprotein cholesterol (HDL-C) (orange), triglycerides (log(TG)) (blue), and apolipoprotein B (Apo B) (pink) were compared among patients with pathogenic or likely pathogenic LIPC variants (n = 10) and normal controls (n = 72). The pathogenic classification was obtained using the AI predictive software VARITY (v1.0). All samples scored 0.823 or higher, with scores closer to 1.00 indicating a higher likelihood of pathogenicity. The darker color corresponds to the LIPC cohort, the lighter to the control. Unpaired one-tailed t-tests were used to compare the lipid levels between cohorts, ‘*’ denotes a p-value < 0.05: TC p = 1.9 × 10−3, LDL-C p = 0.061, HDL-C p = 0.075, log(TG) p = 6.0 × 10−3, and Apo B p = 0.31.

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  Figure 6. Lipid levels of patients with LIPC and familial hypercholesterolemia variants. Plasma lipid levels were compared among patients with both LIPC and familial hypercholesterolemia (FH) variants (n = 7) (purple) and patients with only LIPC variants (n = 46) (pink) or only FH variants (n = 135) (blue). (A) Total cholesterol (TC). The p-value between the LIPC and FH + LIPC groups is p = 0.003. (B) Low-density lipoprotein cholesterol (LDL-C). The one-tailed p-value between LIPC and FH + LIPC is p = 0.002. (C) High-density lipoprotein cholesterol (HDL-C). (D) Log(triglycerides) (log(TG)). ‘*’ denotes a p-value < 0.05. All other comparisons had p-values greater than 0.1.