Mutations Explain Only Some Familial Hypercholesterolemia

Findings support position that the phenotype matters more than the genotype, editorialists note

FRIDAY, Sept. 8 (HealthDay News) -- Only about half of patients with familial hypercholesterolemia (FH) carry a mutation in the LDL-receptor gene, and their clinical and laboratory characteristics differ from FH patients who don't carry a mutation, according to a study published in the September issue of the European Heart Journal.

Emily S. van Aalst-Cohen, M.D., of the University of Amsterdam in the Netherlands, and colleagues randomly selected 4,000 hypercholesterolemic patients from the Dutch Lipid Clinic network database and identified 2,400 of them as having FH.

The researchers found that 52.3 percent of the 2,400 patients carried an LDL-receptor gene mutation and that LDL levels were higher in those who carried the mutation. They also found that triglycerides were higher in patients without a mutation, suggesting that other causes are responsible for their dyslipidemia.

"The genetic background for disease has turned out to be more complex than we thought when the LDL receptor was discovered more than 30 years ago," state the authors of an accompanying editorial. "Since then the prospect that an analysis of the DNA sequence could provide us with unequivocal answers to complex clinical issues has receded steadily. Messy as it is, it's the phenotype that matters, be it dyslipidemia or cardiomyopathy, not the genotype, and, in diagnosing patients and making treatment decisions, there is no real substitute for good clinical judgment."

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