title: Prevalence and clinical features of heterozygous carriers of autosomal recessive hypercholesterolemia in Sardinia.
abstract: 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.
authors.affiliation: Hypertension and Cardiovascular Prevention Center, University of Sassari, Sassari, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Filigheddu
authors.forename: Fabiana
authors.initials: F
authors.lastname: Quagliarini
authors.forename: Filomena
authors.initials: F
authors.lastname: Campagna
authors.forename: Tanuccia
authors.initials: T
authors.lastname: Secci
authors.forename: Simona
authors.initials: S
authors.lastname: Degortes
authors.forename: Roberta
authors.initials: R
authors.lastname: Zaninello
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Argiolas
authors.forename: Roberto
authors.initials: R
authors.lastname: Verna
authors.forename: Silvia
authors.initials: S
authors.lastname: Pitzoi
authors.forename: Francesca
authors.initials: F
authors.lastname: Frau
authors.forename: Chiara
authors.initials: C
authors.lastname: Troffa
authors.forename: Emanuela
authors.initials: E
authors.lastname: Bulla
authors.forename: Stefano
authors.initials: S
authors.lastname: Bertolini
authors.forename: Nicola
authors.initials: N
authors.lastname: Glorioso
authors.forename: Marcello
authors.initials: M
authors.lastname: Arca
mesh_terms: 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
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D008078:Cholesterol, LDL; C469745:LDLRAP1 protein, human