Key result
Lipochip testing identifies causative LDLR mutations in ~20% of familial combined hyperlipidemia patients.
Why the study?
The lipid phenotype frequently overlaps in familial hypercholesterolemia and familial combined hyperlipidemia (FCH), and genetic testing for causative mutations in the LDLR or APOB genes had not been systematically performed in consecutive patients with a clinical diagnosis of FCH.
What is the frequency of LDLR and APOB gene mutations in consecutive patients clinically diagnosed with familial combined hyperlipidemia using microarray screening?
Cross-Sectional (n=143)
What is the frequency of LDLR and APOB gene mutations in consecutive patients clinically diagnosed with familial combined hyperlipidemia using microarray screening?
Answers are grounded in this paper and cite their sources.
Nearly 20% of patients clinically diagnosed with familial combined hyperlipidemia actually harbor causative LDLR mutations indicative of familial hypercholesterolemia, supporting genetic screening in FCH patients with total cholesterol ≥335 mg/dl or apoB ≥185 mg/dl.
OBJECTIVES The purpose of this study was to determine the frequency of mutations in the low-density lipoprotein receptor (LDLR) and apolipoprotein B (APOB) genes in consecutive patients with a clinical diagnosis of familial combined hyperlipidemia (FCH) in a nonresearch setting. BACKGROUND The lipid phenotype frequently overlaps in familial hypercholesterolemia (FH) and FCH. Detection of causative mutations in LDLR or APOB provides an unequivocal diagnosis of FH, but such genetic testing has not been systematically performed in FCH. METHODS We used Lipochip (Progenika, Derio, Spain), a microarray that includes 203 causative mutations in LDLR and 4 APOB defects, to investigate 143 unrelated FCH patients. RESULTS Mutations of LDLR were found in 28 patients (overall prevalence, 19.6%). No APOB defects were found. Compared with patients who had a normal LDLR gene, patients with mutations had lower waist circumference (p = 0.02); significantly (p < 0.005) higher total cholesterol, non-high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and apoB; nonsignificantly (p = 0.063) lower triglycerides; and a lower frequency of diabetes mellitus (22% vs. 0%, respectively; p = 0.002). Total cholesterol and apoB levels showed the best receiver-operator characteristics curves in the prediction of LDLR mutations, with areas under the curve (95% CI: of 0.750 (95% confidence interval [CI]: 0.647 to 0.853) and 0.744 (95% CI: 0.636 to 0.851), respectively. Total cholesterol of 335 mg/dl and apoB of 185 mg/dl were the best thresholds for diagnosis of LDLR mutations. CONCLUSIONS Screening for LDLR defects is advisable for patients with a clinical diagnosis of FCH showing high total cholesterol or apoB levels. Diagnostic criteria for FH should not exclude patients whose personal and familial lipid values appear to fit the clinical criteria of FCH.
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Civeira et al. (2008) conducted a cross-sectional in Familial combined hyperlipidemia (FCH) (n=143). Lipochip genetic testing (203 LDLR mutations and 4 APOB defects) vs. Normal LDLR gene was evaluated on Prevalence of causative mutations in LDLR and APOB genes. Lipochip microarray testing identified causative LDLR gene mutations in 19.6% (28/143) of patients clinically diagnosed with familial combined hyperlipidemia, with no APOB defects found.
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