LPL – Familial Combined Hyperlipidemia

The lipoprotein lipase (LPL) gene has been implicated in familial combined hyperlipidemia (Familial Combined Hyperlipidemia). In a cohort of 93 FCH patients (PMID:19335919) and 286 controls (PMID:19335919), the N291S polymorphism (c.953A>G (p.Asn318Ser)) was detected in 9.7% of cases (PMID:19335919) but absent in controls, and carriers exhibited a predominance of small, dense LDL (pattern B LDL) (87.5% vs 30.8%) (PMID:19335919). This variant frequency aligns with previous reports of 9.3% in Dutch FCH patients and exceeds the 2–5% prevalence observed in other Caucasian populations (PMID:19335919). Although functional studies of other LPL mutations (e.g., splice-site variants and missense substitutions leading to complete loss of enzyme activity) establish that haploinsufficiency drives severe hyperlipidemic phenotypes (PMID:2121025, PMID:1702428), the direct impact of N291S on LPL activity and FCH pathogenesis remains uncharacterized. No family segregation data have been reported. Overall, the evidence is currently limited by the absence of replication and functional assessment of the N291S variant. Key take-home: LPL c.953A>G (p.Asn318Ser) is a potential risk allele for familial combined hyperlipidemia and marker of an atherogenic lipoprotein profile but requires further validation for clinical use.

References

• Lipids in health and disease • 2009 • Small and dense LDL in familial combined hyperlipidemia and N291S polymorphism of the lipoprotein lipase gene. PMID:19335919
• American journal of human genetics • 1990 • Compound heterozygote for lipoprotein lipase deficiency: Ser----Thr244 and transition in 3' splice site of intron 2 (AG----AA) in the lipoprotein lipase gene. PMID:2121025
• The Journal of biological chemistry • 1991 • Identification of two separate allelic mutations in the lipoprotein lipase gene of a patient with the familial hyperchylomicronemia syndrome. PMID:1702428

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