1. Platelet-activating factor acetylhydrolase gene polymorphism and its activity in Japanese patients with multiple sclerosis
- Author
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Kunio Tashiro, Hirofumi Ochi, Toshiyuki Fukazawa, Masaaki Niino, Hiroyuki Murai, Seiji Kikuchi, Jun Ichi Kira, Manabu Osoegawa, and Motozumi Minohara
- Subjects
Adult ,Male ,medicine.medical_specialty ,Multiple Sclerosis ,Genotype ,Immunology ,Mutation, Missense ,Biology ,Severity of Illness Index ,Asian People ,Gene Frequency ,Internal medicine ,medicine ,PLATELET-ACTIVATING FACTOR ACETYLHYDROLASE ,Humans ,Immunology and Allergy ,Missense mutation ,Gene Silencing ,Allele ,Gene ,Alleles ,Polymerase ,Polymorphism, Genetic ,Multiple sclerosis ,Neuromyelitis Optica ,Middle Aged ,medicine.disease ,Molecular biology ,Enzyme Activation ,Endocrinology ,Neurology ,1-Alkyl-2-acetylglycerophosphocholine Esterase ,biology.protein ,Female ,Neurology (clinical) ,Gene polymorphism - Abstract
We evaluated the association of the plasma platelet-activating factor acetylhydrolase (PAF-AH) gene polymorphism (G994→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 G994→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.
- Published
- 2004