FH-causing mutations have an estimated prevalence of 1 in 217 (0.46%) in the general population and are best identified by definite/probable DLCN criteria or LDL-cholesterol >4.4 mmol/L.
Cross-Sectional (n=98,098)
What is the prevalence and what are the predictors of familial hypercholesterolaemia-causing mutations in the general population?
Familial hypercholesterolaemia-causing mutations are more common than previously thought, occurring in approximately 1 in 217 individuals in the general population, and are best identified using DLCN criteria or an LDL-C >4.4 mmol/L.
Effect estimate: OR 439 (95% CI 170-1138)
AIMS: Ideally, familial hypercholesterolaemia (FH) is diagnosed by testing for mutations that decrease the catabolism of low-density lipoprotein (LDL) cholesterol; however, genetic testing is not universally available. The aim of the present study was to assess the frequency and predictors of FH causing mutations in 98 098 participants from the general population, the Copenhagen General Population Study. METHODS AND RESULTS: We genotyped for LDLRW23X;W66G;W556S and APOBR3500Q accounting for 38.7% of pathogenic FH mutations in Copenhagen. Clinical FH assessment excluded mutation information. The prevalence of the four FH mutations was 0.18% (1:565), suggesting a total prevalence of FH mutations of 0.46% (1:217). Using the Dutch Lipid Clinic Network (DLCN) criteria, odds ratios for an FH mutation were 439 (95% CI: 170-1 138) for definite FH, 90 (53-152) for probable FH, and 18 (13-25) for possible FH vs. unlikely FH. Using the Simon Broome criteria, the odds ratio was 27 (20-36) for possible vs. unlikely FH, and using the Make Early Diagnosis to Prevent Early Death (MEDPED) criteria, 40 (28-58) for probable vs. unlikely FH. Odds ratios for an FH mutation were 17 (9-31) for LDL-cholesterol of 4-4.9 mmol/L, 69 (37-126) for LDL-cholesterol of 5-5.9 mmol/L, 132 (66-263) for LDL-cholesterol of 6-6.9 mmol/L, 264 (109-637) for LDL-cholesterol of 7-7.9 mmol/L, and 320 (129-798) for LDL-cholesterol above 7.9 mmol/L vs. LDL-cholesterol below 4 mmol/L. The most optimal threshold for LDL-cholesterol concentration to discriminate between mutation carriers and non-carriers was 4.4 mmol/L. CONCLUSION: Familial hypercholesterolaemia-causing mutations are estimated to occur in 1:217 in the general population and are best identified by a definite or probable phenotypic diagnosis of FH based on the DLCN criteria or an LDL-cholesterol above 4.4 mmol/L.
Benn et al. (2016) conducted a cross-sectional in Familial hypercholesterolaemia (n=98,098). Genotyping for LDLR and APOB mutations vs. Non-carriers was evaluated on Frequency and predictors of FH causing mutations (OR 439, 95% CI 170-1138). FH-causing mutations have an estimated prevalence of 1 in 217 (0.46%) in the general population and are best identified by definite/probable DLCN criteria or LDL-cholesterol >4.4 mmol/L.