PMID- 30694883
OWN - NLM
STAT- MEDLINE
DCOM- 20200220
LR  - 20200220
IS  - 1744-6880 (Electronic)
IS  - 1744-6872 (Linking)
VI  - 29
IP  - 4
DP  - 2019 Jun
TI  - Associations between TMEM196 polymorphisms and NSAID-exacerbated respiratory 
      disease in asthma.
PG  - 69-75
LID - 10.1097/FPC.0000000000000367 [doi]
AB  - BACKGROUND: We previously found differences in the minor allele frequency (MAF) 
      of single-nucleotide polymorphisms (SNPs) in transmembrane protein 196 (TMEM196) 
      between 995 patients with aspirin-tolerant asthma (ATA) and 141 asthmatic 
      patients with NSAID-exacerbated respiratory disease (NERD). In this study, we 
      statistically analyzed the distributions of the genotypes and haplotypes of these 
      SNPs to determine the exact association between TMEM196 genetic variants and the 
      risk for NERD. MATERIALS AND METHODS: Lewontin's D' and r values were used to 
      measure linkage disequilibrium between the biallelic loci having MAFs more than 
      0.05, and haplotypes were inferred using the PHASE algorithm (version 2.0). The 
      genotype distribution was analyzed by logistic regression models using age of 
      onset, smoking status (nonsmoker=0, ex-smoker=1, smoker=2), and BMI as 
      covariates. Regression analysis of the association between SNPs and the risk of 
      NERD was analyzed using SPSS version 12.0 and PLINK version 1.9. RESULTS: The MAF 
      of rs9886152 C>T was significantly lower in NERD than in ATA [24.8 vs. 34.0%, 
      odds ratio=0.64 (0.48-0.85), P=2.07x10, Pcorr=0.048]. The rate of the rs9886152 
      C>T minor allele was significantly lower in NERD than in ATA [44.0 vs. 56.4% in 
      the codominant model, P=0.002, Pcorr=0.049, odds ratio=0.64 (0.48-0.85)]. An 
      additional three SNPs (rs9639334 A>G, rs9638765 A>G, and rs2097811 G>A) showed 
      similar associations with the risk of NERD. NERD patients had lower frequencies 
      of the rs9639334 A>G minor allele (51.1 vs. 64.4%, P=0.002, Pcorr=0.043), 
      rs9638765 A>G (49.7 vs. 64.2%, P=0.001, Pcorr=0.017), and rs2097811 G>A (51.1 vs. 
      64.5%, P=0.002, Pcorr=0.04) compared with ATA patients. Patients homozygous for 
      the minor alleles of the four SNPs showed significantly less of an 
      aspirin-induced decrease in forced expiratory volume in one second compared with 
      those homozygous for the common alleles (P=0.003-0.012). CONCLUSION: The minor 
      alleles of the four SNPs in TMEM196 may exert a protective effect against the 
      development of NERD and may be useful genetic markers to predict the risk of 
      NERD.
FAU - Lee, Jong-Uk
AU  - Lee JU
AD  - Department of Medical Bioscience, Graduate School, Soonchunhyang University, 
      Asan.
FAU - Chang, Hun Soo
AU  - Chang HS
AD  - Department of Medical Bioscience, Graduate School, Soonchunhyang University, 
      Asan.
AD  - Department of Internal Medicine, Division of Allergy and Respiratory Medicine, 
      Soonchunhyang University Bucheon Hospital, Bucheon.
FAU - Baek, Dong Gyu
AU  - Baek DG
AD  - Department of Medical Bioscience, Graduate School, Soonchunhyang University, 
      Asan.
FAU - Shin, Hyoung Doo
AU  - Shin HD
AD  - Department of Genetic Epidemiology, SNP Genetics Inc.
AD  - Department of Life Science, Sogang University, Seoul, Republic of Korea.
FAU - Park, Choon-Sik
AU  - Park CS
AD  - Department of Medical Bioscience, Graduate School, Soonchunhyang University, 
      Asan.
AD  - Department of Internal Medicine, Division of Allergy and Respiratory Medicine, 
      Soonchunhyang University Bucheon Hospital, Bucheon.
FAU - Park, Jong-Sook
AU  - Park JS
AD  - Department of Medical Bioscience, Graduate School, Soonchunhyang University, 
      Asan.
AD  - Department of Internal Medicine, Division of Allergy and Respiratory Medicine, 
      Soonchunhyang University Bucheon Hospital, Bucheon.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pharmacogenet Genomics
JT  - Pharmacogenetics and genomics
JID - 101231005
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Membrane Proteins)
RN  - 0 (TMEM196 protein, human)
RN  - R16CO5Y76E (Aspirin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anti-Inflammatory Agents, Non-Steroidal/adverse effects
MH  - Aspirin/administration & dosage/*adverse effects
MH  - Asthma, Aspirin-Induced/*genetics/pathology
MH  - Female
MH  - Forced Expiratory Volume
MH  - Gene Frequency
MH  - *Genetic Association Studies
MH  - Genotype
MH  - Haplotypes/genetics
MH  - Homozygote
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Male
MH  - Membrane Proteins/*genetics
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide/genetics
EDAT- 2019/01/30 06:00
MHDA- 2020/02/23 06:00
CRDT- 2019/01/30 06:00
PHST- 2019/01/30 06:00 [pubmed]
PHST- 2020/02/23 06:00 [medline]
PHST- 2019/01/30 06:00 [entrez]
AID - 10.1097/FPC.0000000000000367 [doi]
PST - ppublish
SO  - Pharmacogenet Genomics. 2019 Jun;29(4):69-75. doi: 10.1097/FPC.0000000000000367.