LIPI – Hypertriglyceridemia

LIPI encodes a membrane-associated lipase implicated in triglyceride metabolism. In a cohort of hypertriglyceridemic subjects, two unrelated individuals were heterozygous for a rare c.164G>A (p.Cys55Tyr) variant in LIPI, which was absent from 600 control chromosomes (PMID:12719377). No segregation data are available, and inheritance is presumed autosomal dominant based on heterozygous occurrence without biallelic loss.

Functional disruption of the mouse Lpdl ortholog via exon 10 insertion leads to elevated plasma triglycerides and hepatic steatosis, recapitulating key aspects of human hypertriglyceridemia and supporting a haploinsufficiency mechanism (PMID:12719377). Additional studies describing alternative LIPI transcript variants in Ewing tumor cells suggest complex regulation but do not directly address lipid phenotype (PMID:21132378). Overall, human genetic evidence remains limited and requires further replication in larger cohorts for diagnostic validation.

Key Take-home: Rare heterozygous LIPI variants may contribute to hypertriglyceridemia, but current evidence is limited and additional human studies are needed to confirm clinical utility.

References

• Human molecular genetics • 2003 • Identification of a novel lipase gene mutated in lpd mice with hypertriglyceridemia and associated with dyslipidemia in humans. PMID:12719377
• Molecular biology reports • 2011 • Expression of multiple membrane-associated phospholipase A1 beta transcript variants and lysophosphatidic acid receptors in Ewing tumor cells. PMID:21132378

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