Association of sick building syndrome with neuropathy target esterase (NTE) activity in Japanese

• Published in: Environmental toxicology 2014-10, Vol.29 (10), p.1217-1226
• Main Authors: Matsuzaka, Yasunari, Ohkubo, Tomoichi, Kikuti, Yukie Y, Mizutani, Akiko, Tsuda, Michio, Aoyama, Yoshiko, Kakuta, Kazuhiko, Oka, Akira, Inoko, Hidetoshi, Sakabe, Kou, Ishikawa, Satoshi, Kulski, Jerzy K, Kimura, Minoru
• Format: Article
• Language: English
• Subjects: Adult; Asian Continental Ancestry Group - genetics; Carboxylic Ester Hydrolases - genetics; Carboxylic Ester Hydrolases - metabolism; Case-Control Studies; enzyme activity; Female; gene frequency; genes; genotype; Humans; introns; Leukocytes, Mononuclear - enzymology; Leukocytes, Mononuclear - metabolism; Male; microsatellite; Microsatellite Repeats; Middle Aged; mononuclear leukocytes; nerve tissue; NTE; organophosphorus compounds; patients; peripheral nervous system diseases; Phospholipases - genetics; Phospholipases - metabolism; PNPLA6; Polymorphism, Single Nucleotide; serine; sick building syndrome; Sick Building Syndrome - enzymology; Sick Building Syndrome - genetics; Sick Building Syndrome - metabolism; single nucleotide polymorphism; SNPs; Young Adult
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.21839

Sick building syndrome (SBS) is a set of several clinically recognizable symptoms reported by occupants of a building without a clear cause. Neuropathy target esterase (NTE) is a membrane bound serine esterase and its reaction with organophosphates (OPs) can lead to OP‐induced delayed neuropathy (OPIDN) and nerve axon degeneration. The aim of our study was to determine whether there was a difference in NTE activity in the peripheral blood mononuclear cells (PBMCs) of Japanese patients with SBS and healthy controls and whether PNPLA6 (alias NTE) gene polymorphisms were associated with SBS. We found that the enzymatic activity of NTE was significantly higher (P < 0.0005) in SBS patients compared with controls. Moreover, population with an AA genotype of a single nucleotide polymorphism (SNP), rs480208, in intron 21 of the PNPLA6 gene strongly reduced the activity of NTE. Fifty‐eight SNP markers within the PNPLA6 gene were tested for association in a case–control study of 188 affected individuals and 401 age‐matched controls. Only one SNP, rs480208, was statistically different in genotype distribution (P = 0.005) and allele frequency (P = 0.006) between the cases and controls (uncorrected for testing multiple SNP sites), but these were not significant by multiple corrections. The findings of the association between the enzymatic activity of NTE and SBS in Japanese show for the first time that NTE activity might be involved with SBS. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1217–1226, 2014.