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Contribution of the N-acetyltransferase 2 polymorphism NAT2*6A to age-related hearing impairment


Background: Age-related hearing impairment (ARHI) is the most common sensory impairment in older people, affecting 50% of those aged 80 years. The proportion of older people is increasing in the general population, and as a consequence, the number of people affected with ARHI is growing. ARHI is a complex disorder, with both environmental and genetic factors contributing to the disease. The first studies to elucidate these genetic factors were recently performed, resulting in the identification of the first two susceptibility genes for ARHI, NAT2 and KCNQ4.

Methods: In the present study, the association between ARHI and polymorphisms in genes that contribute to the defence against reactive oxygen species, including GSTT1, GSTM1 and NAT2, was tested. Samples originated from seven different countries and were combined into two test population samples, the general European population and the Finnish population. Two distinct phenotypes for ARHI were studied, Zlow and Zhigh, representing hearing in the low and high frequencies, respectively. Statistical analysis was performed for single polymorphisms (GSTM1, GSTT1, NAT2*5A, NAT2*6A, and NAT2*7A), haplotypes, and gene–environment and gene–gene interactions.

Results: We found an association between ARHI and GSTT1 and GSTM1 in the Finnish population sample, and with NAT2*6A in the general European population sample. The latter finding replicates previously published data.

Conclusion: As replication is considered the ultimate proof of true associations in the study of complex disorders, this study provides further support for the involvement of NAT2*6A in ARHI.

  • ARHI, age-related hearing impairment
  • FDR, false discovery rate
  • GSH, glutathione
  • GSR, glutathione reductase
  • GST, glutathione S-transferase
  • GSTP1, glutathione S transferase ρ
  • GXP1, glutathione peroxidase 1
  • ROS, reactive oxygen species
  • SOD1, superoxide dismutase 1
  • SNP, single nucleotide polymorphism
  • N-acetyltransferase
  • age related hearing impairment
  • association study
  • complex disorder
  • glutathione S-transferase

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