Familial hypercholesterolemia study in Sardinia using 6 LDLR polymorphic markers based on PCR

Twenty-two Sardinian families with multiple cases of hypercholesterolemia w ere investigated with six polymorphic markers of the low-density lipoprotei n receptor (LDLR) gene that could be quickly analyzed by PCR-based methods. Five single nucleotide polymorphisms (SNP) in exons 8, 10, 13, 15, and 18 and a microsatellite marker flanking the 3' end of the LDLR gene were used to define the haplotypes at the LDLR locus for familial hypercholesterolemi a (FH) diagnosis within families. No significant differences were observed between the allele frequencies of the normal and mutant chromosomes. In two families, hypercholesterolemia did not cosegregate with the LDLR locus, In the remaining 20 FH chromosomes, seven different haplotypes were identifie d. The same haplotypes were found with a similar frequency among the 61 nor mal chromosomes. Other five haplotypes were characteristic only of normal c hromosomes. These data provide no evidence for a gene founder effect in the Sardinian population and, instead, highlight a pattern of genetic heteroge neity comparable with that found in mainland European populations. The repl acement of the restriction fragment length polymorphisms currently used in the genetic analysis of FH with PCR-based markers proved to be a simple and less time-consuming method and did not reduce informativity in the molecul ar analysis of FH families. (C) 2000 Wiley-Liss, Inc.