title: Platelet-activating factor acetylhydrolase gene polymorphism and its activity in Japanese patients with multiple sclerosis.
abstract: We evaluated the association of the plasma platelet-activating factor acetylhydrolase (PAF-AH) gene polymorphism (G(994)-->T) and PAF-AH activity with susceptibility and severity of multiple sclerosis (MS) in Japanese. DNA was collected from 216 patients with clinically definite MS (65 opticospinal MS (OS-MS) and 151 conventional MS (C-MS)) and from 213 healthy controls. The missense mutation G(994)-->T that disrupts the PAF-AH activity was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). No statistically significant difference in the frequency of genotypes and alleles of the plasma PAF-AH polymorphism was observed among OS-MS patients, C-MS patients and healthy controls. However, the missense mutation tended to be associated with the severity of OS-MS, especially in females (GT/TT genotypes; 51.7% in female rapidly progressive OS-MS vs. 26.6% in female controls, p=0.0870). Moreover, PAF-AH activities were significantly lower in MS than in controls, irrespective of clinical subtypes, among those carrying the identical polymorphism in terms of nucleotide position 994 of the PAF-AH gene. These findings suggest that the PAF-AH gene missense mutation has no relation to either susceptibility or severity of C-MS, yet its activity is down-regulated, and that the mutation has no relation with susceptibility of OS-MS, yet it may confer the severity of female OS-MS.
authors.affiliation: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Osoegawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Niino
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ochi
authors.forename: Seiji
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Murai
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukazawa
authors.forename: Motozumi
authors.initials: M
authors.lastname: Minohara
authors.forename: Kunio
authors.initials: K
authors.lastname: Tashiro
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Kira
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D000483:Alleles; D044466:Asian People; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020868:Gene Silencing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D020125:Mutation, Missense; D009471:Neuromyelitis Optica / Q000201:enzymology / Q000235:genetics; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index
chemical_list: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase