Prevalence and clinical features of heterozygous carriers of autosomal recessive hypercholesterolemia in Sardinia.
OBJECTIVE
Autosomal recessive hypercholesterolemia (ARH) is a lipid disorder caused by mutations in a specific adaptor protein for the LDL receptor. ARH is rare except in Sardinia where three alleles (ARH1, ARH2 and ARH3) explain most of cases. The prevalence of ARH heterozygotes in Sardinia is not well determined as well as inconclusive data are available on the effect of the ARH carrier status on LDL cholesterol (LDL-C) and coronary risk.


METHODS
3410 Sardinians (986 blood donors, 1709 with hypertension and 715 with myocardial infarction (MI)) were screened for ARH alleles. For comparison purposes, lipid data of 60 ARH heterozygous carriers and 60 non-carriers identified within 24 ARH families were also considered.


RESULTS
In the whole study cohort, no ARH homozygotes were found, but 15 ARH1 (0.44%) and 9 ARH2 (0.26%) heterozygous carriers were identified. The frequency of ARH alleles in blood donors was 0.0030, not different from that in hypertensive subjects (0.0032). ARH alleles tended to be more common in MI patients (0.0049), but no association between ARH carrier status and MI risk was detected after controlling for conventional risk factors. ARH carriers and non-carriers showed similar LDL-C levels. This result was confirmed when ARH carriers and non-carriers identified throughout family-based and population-based screenings were combined and compared (141.0+/-41 mg/dl vs. 137.0+/-41 mg/dl, respectively; p=0.19).


CONCLUSIONS
These data indicate that the frequency of ARH heterozygotes in Sardinia is approximately 1:143 individuals, thus making this condition one of the most common in the Sardinian population. However, ARH carrier status does not influence LDL-C concentration and coronary risk, thus suggesting that ARH can be regarded as a truly recessive disorder.
Filigheddu
Fabiana
F
Hypertension and Cardiovascular Prevention Center, University of Sassari, Sassari, Italy.
Quagliarini
Fabiana
F
Campagna
Filomena
F
Secci
Tanuccia
T
Degortes
Simona
S
Zaninello
Roberta
R
Argiolas
Giuseppe
G
Verna
Roberto
R
Pitzoi
Silvia
S
Frau
Francesca
F
Troffa
Chiara
C
Bulla
Emanuela
E
Bertolini
Stefano
S
Glorioso
Nicola
N
Arca
Marcello
M
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D007558:Italy / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D008078:Cholesterol, LDL; C469745:LDLRAP1 protein, human