Homozygous familial hypercholesterolemia in Lebanon: A genotype/phenotype correlation

Familial hypercholesterolemia (FH) is an inherited disease characterized by the deposition of LDL in tissues causing premature atherosclerosis. Many genes are implicated in FH resulting in a large variability in the phenotype. DNA sequencing of the LDLR gene was done for forty patients clinically di...

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Bibliographic Details
Published in:Molecular genetics and metabolism 2011-02, Vol.102 (2), p.181-188
Main Authors: Fahed, Akl C., Safa, Raya M., Haddad, Fadi F., Bitar, Fadi F., Andary, Rabih R., Arabi, Mariam T., Azar, Sami T., Nemer, Georges
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Child
Cholesterol, LDL - blood
Female
Genetic Association Studies
Genotype
Heart
Homozygote
Humans
Hypercholesterolemia
Hyperlipoproteinemia Type II - epidemiology
Hyperlipoproteinemia Type II - genetics
LDLR
Lebanon - epidemiology
Male
Middle Aged
Molecular Typing
Mutation
Mutation - genetics
Pedigree
Receptors, LDL - genetics
Young Adult
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Summary:Familial hypercholesterolemia (FH) is an inherited disease characterized by the deposition of LDL in tissues causing premature atherosclerosis. Many genes are implicated in FH resulting in a large variability in the phenotype. DNA sequencing of the LDLR gene was done for forty patients clinically diagnosed with homozygous FH and forty family members variably affected. Patients underwent noninvasive heart and vascular studies. Statistical and pedigree analyses were used to correlate the different genotypes with the phenotypes. The prevalence of homozygosity at the Lebanese allele (2043 C>A) is 45%. However, 27.5% of the patients have no mutations at all in the LDLR gene, and 27.5% are either heterozygous for the 2043 C>A mutation, heterozygous for a mutation in another exon of the LDLR gene, or combined heterozygous for two different mutations. We confirm previous reports on the higher prevalence of FH in Lebanon. Our results do, however contradict previous reports on an assumed higher prevalence among the Christian Lebanese. Mutations in the LDLR especially combined heterozygosity can cause a severe phenotype similar to the homozygous mutation in the Lebanese allele. This information is particularly important in targeting the more prevalent heterozygotes in the general population with early diagnosis and intervention.
ISSN:1096-7192
1096-7206
DOI:10.1016/j.ymgme.2010.11.006