Contribution of Rare and Common APOE Variants to Familial Hypercholesterolemia in Spanish Cohort
Abstract
:1. Introduction
2. Patients, Controls, and Methods
2.1. Study Population
2.2. Genetic Testing for Pathogenic Variants
2.3. APOE Genotyping
2.4. Statistical Analysis
3. Results
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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FH Patients N = 431 | Controls N = 165 | |
---|---|---|
Men | 227 (53%) | 78 (47%) |
Women | 204 (47%) | 87 (53%) |
Age at diagnostic range years | 18–45 | 18–60 |
Total cholesterol mG/dL mean (range) | 345 (275–926) | 205 (78–310) |
LDL-cholesterol mean (range) | 248 (180–750) | 132 (61–150) |
Triglycerides | 194 (15–1132) | 97 (28–320) |
DLCN score | ||
3–5 possible | 25% | - |
6–8 probable | 40% | - |
>8 definite | 35% | - |
Gene/Variant | Npatients |
---|---|
APOB: c.10580G>A (p.Arg3527Gln) | 2 |
APOE: c.500_502del (p.Leu167del) | 3 |
APOE: c.83C>T(p.Pro28leu) | 1 |
LDLR: c.91G>T (p.Glu31Ter) | 2 |
LDLR: c.251C>T (p.Pro84Leu) | 1 |
LDLR: c.409G>A (p.Gly137Ser) | 1 |
LDLR: c.464G>A (p.Cys155Tyr) | 2 |
LDLR: c.487C>T (p.Gln163Ter) | 1 |
LDLR: c.520G>A (p.Glu174Ter) | 1 |
LDLR: c.530C>T (p.Ser177Leu) | 3 |
LDLR: c.676T>C (p.Ser226Pro) | 1 |
LDLR: c.682G>A (p.Glu228Lys) | 1 |
LDLR: c.758G>A (p.Arg253Gln) | 1 |
LDLR: c.682G>A (p.Glu288Lys) | 1 |
LDLR: c.889A>C (p.Asn297His) | 1 |
LDLR: c.916_919dupTCAG (p.Asp307Valfs*3) | 1 |
LDLR: c.1019G>A (p.Cys340Tyr) | 1 |
LDLR: c.1060G>A (p.Asp354Asn) | 1 |
LDLR: c.1176C>A (p.Cys392Ter) | 1 |
LDLR: c.1216C>T (p.Arg406Trp) | 3 |
LDLR: c.1222G>A (p.Glu408Lys) | 1 |
LDLR: c.1246C>T (p.Arg416Trp) | 4 |
LDLR: c.1285G>A (p.Val429Met) | 23 |
LDLR:c.1609G>T (p.Gly537Ter) | 1 |
LDLR: c.1690A>C (p.Asn564His) | 1 |
LDLR: c.1775G>A (p.Gly592Glu) | 11 |
LDLR: c.1796T>C (p.Leu599Ser) | 4 |
LDLR: c.1804G>T (p.Glu602Ter) | 1 |
LDLR: c.1816G>T (p.Ala606Ser) | 2 |
LDLR: c.1862C>T (p.Thr621Ile) | 1 |
LDLR: c.1897C>T (p.Arg633Cys) | 2 |
LDLR:c.1898G>A (p.Arg633His) | 5 |
LDLR:c.1966C>A (p.His656Asn) | 2 |
LDLR: c.1973T>C (p.Leu658Pro) | 1 |
LDLR: c.2096C>T (p.Pro699Leu) | 3 |
LDLR: c.2099A>G (p.Asp700Gly) | 1 |
LDLR: c.2177C>T (p.Thr726Ile) | 2 |
LDLR: c.2397_2405del (p.Val800_Leu802del) | 1 |
LDLR: c. 7+1G>T (IVS1+1G>T) | 7 |
LDLR: c.1987+1 G>A (IVS13+1G>A) | 1 |
LDLR: c.1988−2 A>T (IVS13−2A>T) | 1 |
LDLR: c.2389+4 A>G (IVS16+4A>G) | 27 |
LDLR: c.313+2 insT (IVS3+2insT) | 5 |
LDLR: c.1186+5 G>A (IVS8+5G>A) | 1 |
LDLR: c.1187+1delG (IVS8−1delG) | 1 |
LDLRAP1: c.207delC (p.Ala70ProfsTer19) HOMOZYGOUS | 1 |
PV POS N = 139 | PV NEG N = 292 | Controls N = 165 | |
---|---|---|---|
AGE at diagnostic range in years | 18–40 | 25–45 | 18–60 |
MALE | 76 (55%) | 151 (52%) | 78 (47%) |
FEMALE | 63 (45%) | 141 (48%) | 87 (53%) |
LDL-C range mG/dL | 190–750 | 180–358 | 61–150 |
LDL-C mean mG/dL | 268 | 213 | 132 |
APOE-e2/e3/e4 | |||
e2e2 | 0 | 1 | 0 |
e2e3 | 9 (6%) | 14 (5%) | 26 (16%) |
e2e4 | 1 | 0 | 2 (1%) |
e3e3 | 106 (76%) | 193 (66%) | 115 (70%) |
e3e4 | 23 (17%) | 71 (24%) | 20 (12%) |
e4e4 | 0 | 13 (4%) | 2 (1%) |
e3e4 + e4e4 | 23 (17%) | 84 (29%) | 22 (13%) |
e4 | 0.09 | 0.17 | 0.08 |
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Vega-Prado, L.M.; Vázquez-Coto, D.; Villazón, F.; Suárez-Gutiérrez, L.; Martínez-Faedo, C.; Menéndez-Torre, E.; Riestra, M.; González-Martínez, S.; Gutiérrez-Buey, G.; García-Lago, C.; et al. Contribution of Rare and Common APOE Variants to Familial Hypercholesterolemia in Spanish Cohort. Cardiogenetics 2025, 15, 3. https://doi.org/10.3390/cardiogenetics15010003
Vega-Prado LM, Vázquez-Coto D, Villazón F, Suárez-Gutiérrez L, Martínez-Faedo C, Menéndez-Torre E, Riestra M, González-Martínez S, Gutiérrez-Buey G, García-Lago C, et al. Contribution of Rare and Common APOE Variants to Familial Hypercholesterolemia in Spanish Cohort. Cardiogenetics. 2025; 15(1):3. https://doi.org/10.3390/cardiogenetics15010003
Chicago/Turabian StyleVega-Prado, Lorena M., Daniel Vázquez-Coto, Francisco Villazón, Lorena Suárez-Gutiérrez, Ceferino Martínez-Faedo, Edelmiro Menéndez-Torre, María Riestra, Silvia González-Martínez, Gala Gutiérrez-Buey, Claudia García-Lago, and et al. 2025. "Contribution of Rare and Common APOE Variants to Familial Hypercholesterolemia in Spanish Cohort" Cardiogenetics 15, no. 1: 3. https://doi.org/10.3390/cardiogenetics15010003
APA StyleVega-Prado, L. M., Vázquez-Coto, D., Villazón, F., Suárez-Gutiérrez, L., Martínez-Faedo, C., Menéndez-Torre, E., Riestra, M., González-Martínez, S., Gutiérrez-Buey, G., García-Lago, C., Gómez, J., Alvarez, V., Gil, H., Lorca, R., & Coto, E. (2025). Contribution of Rare and Common APOE Variants to Familial Hypercholesterolemia in Spanish Cohort. Cardiogenetics, 15(1), 3. https://doi.org/10.3390/cardiogenetics15010003