Initial Characterization of the Involvement of LPIN2 in Inflammation
- Author(s): Martinez, Mariela
- Advisor(s): Reue, Karen
- et al.
Lipin-2 (encoded by the LPIN2 gene) is an enzyme that acts in the synthesis of glycerolipids. LPIN2 mutations have been implicated in two distinct autoinflammatory diseases--Majeed syndrome and Familial Mediterranean Fever (FMF)--but its role in these diseases has not been described. I hypothesized that lipin-2 has a role in modulating inflammation in macrophages, and that mutations in LPIN2 may occur in FMF in Mediterranean populations, where FMF is most prevalent.
The effect of inflammatory (endotoxin) and lipotoxic (fatty acid) stimuli was assessed in peritoneal macrophages from wild-type and lipin-2-deficient mice. Differences in the induction of pro-inflammatory cytokines were observed between the two genotypes in response to endotoxin. LPIN2 exon sequencing in MEFV heterozygous FMF patients from Israel identified four LPIN2 variants, but these are not likely to be pathogenic. This suggests that mutations in LPIN2 are not prevalent in FMF in the Israeli population.