Ishihara_2004_J.Hum.Genet_49_302

Reference

Title : Functional impairment of two novel mutations detected in lipoprotein-associated phospholipase A2 (Lp-PLA2) deficiency patients - Ishihara_2004_J.Hum.Genet_49_302
Author(s) : Ishihara M , Iwasaki T , Nagano M , Ishii J , Takano M , Kujiraoka T , Tsuji M , Hattori H , Emi M
Ref : J Hum Genet , 49 :302 , 2004
Abstract : Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2), also known as platelet-activating factor (PAF) acetylhydrolase (PAF-AH), is a member of the serine-dependent class of A2 phospholipases that hydrolyze sn2-ester bonds of fragmented or oxidized phospholipids at sites where atherosclerotic plaques are forming. Most circulating Lp-PLA2 is bound to low-density lipoprotein (LDL) particles in plasma and the rest to high-density lipoprotein (HDL). Deficiency of Lp-PLA2 is a predisposing factor for cardiovascular diseases in the Japanese population. We describe here two novel mutations of the gene encoding Lp-PLA2, InsA191 and I317N in Japanese subjects. The first patient, with partial Lp-PLA2 deficiency, was heterozygous for the InsA191 mutation; macrophages from this patient secreted only half the normal amount of Lp-PLA2 in vitro. The other patient, who showed complete Lp-PLA2 deficiency, was a compound heterozygote for the novel I317N mutation and a common V279F mutation; macrophages from that patient failed to secrete any Lp-PLA2. Measurement of Lp-PLA2 mass, activity and Western blotting verified impaired production and secretion of the enzyme after transfection of mutant construct into COS-7 cells. These results indicated that both novel mutants, InsA191 and I317N, impair function of the Lp-PLA2 gene.
ESTHER : Ishihara_2004_J.Hum.Genet_49_302
PubMedSearch : Ishihara_2004_J.Hum.Genet_49_302
PubMedID: 15148590
Gene_locus related to this paper: human-PLA2G7

Related information

Gene_locus related to this paper: human-PLA2G7

Citations formats

Ishihara M, Iwasaki T, Nagano M, Ishii J, Takano M, Kujiraoka T, Tsuji M, Hattori H, Emi M (2004)
Functional impairment of two novel mutations detected in lipoprotein-associated phospholipase A2 (Lp-PLA2) deficiency patients
J Hum Genet 49 :302

Ishihara M, Iwasaki T, Nagano M, Ishii J, Takano M, Kujiraoka T, Tsuji M, Hattori H, Emi M (2004)
J Hum Genet 49 :302