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The N-acetyltransferase 2 polymorphism NAT2*6A is a causative factor for Age Related Hearing Impairment
  1. Els Van Eyken (els.vaneyken{at}ua.ac.be)
  1. University of Antwerp, Belgium
    1. Guy Van Camp (guy.vancamp{at}ua.ac.be)
    1. University of Antwerp, Belgium
      1. Erik Fransen (erik.fransen{at}ua.ac.be)
      1. University of Antwerp, Belgium
        1. Vedat Topsakal (lazvedat{at}gmail.com)
        1. University Hospital Antwerp, Belgium
          1. Jan Jaap Hendrickx (janjaap.hendrickx{at}ua.ac.be)
          1. University Hospital Antwerp, Belgium
            1. Kelly Demeester (kelly.demeester{at}ua.ac.be)
            1. University Hospital Antwerp, Belgium
              1. Paul Van de Heyning (paul.van.de.heyning{at}uza.be)
              1. University Hospital Antwerp, Belgium
                1. Elina Mäki-Torkko (elina.maki-torkko{at}lio.se)
                1. University of Oulu, Finland
                  1. Samuli Hannula (samuli.hannula{at}oulu.fi)
                  1. University of Oulu, Finland
                    1. Martti Sorri (martti.sorri{at}oulu.fi)
                    1. University of Oulu, Finland
                      1. Mona Jensen (mj21{at}bbh.hosp.dk)
                      1. Bispebjerg Hospital (BBH), Copenhagen, Denmark
                        1. Agnete Parving (ap03{at}bbh.hosp.dk)
                        1. Bispebjerg Hospital (BBH), Copenhagen, Denmark
                          1. Michael Bille (mbille{at}dadlnet.dk)
                          1. Bispebjerg Hospital (BBH), Copenhagen, Denmark
                            1. Manuela Baur (manuela.baur{at}agmx.de)
                            1. University of Tuebingen, Germany
                              1. Marcus Pfister (mpfister{at}onlinehome.de)
                              1. University of Tuebingen, Germany
                                1. Amanda Bonaconsa (amanda.b08{at}libero.it)
                                1. University Hospital Padova, Italy
                                  1. Manuela Mazzoli (manuela.mazzoli{at}sanita.padova.it)
                                  1. University Hospital Padova, Italy
                                    1. Eva Orzan (orzan{at}unipd.it)
                                    1. University Hospital Padova, Italy
                                      1. Angeles Espeso (espesoangeles{at}hotmail.com)
                                      1. University Hospital of Wales, United Kingdom
                                        1. Dafydd Stephens (stephensd{at}cardiff.ac.uk)
                                        1. University Hospital of Wales, United Kingdom
                                          1. Katia Verbruggen (katia.verbruggen{at}ugent.be)
                                          1. University of Ghent, Belgium
                                            1. Joke Huyghe (joke.huyghe{at}ugent.be)
                                            1. University of Ghent, Belgium
                                              1. Ingeborg Dhooghe (ingeborg.dhooghe{at}ugent.be)
                                              1. University of Ghent, Belgium
                                                1. Patrick Huygen (p.huygen{at}kno.umcn.nl)
                                                1. Radboud University Nijmegen, Netherlands
                                                  1. Hannie Kremer (h.kremer{at}antrg.umcn.nl)
                                                  1. Radboud University Nijmegen, Netherlands
                                                    1. Cor Cremers (c.cremers{at}kno.umcn.nl)
                                                    1. Radboud University Nijmegen, Netherlands
                                                      1. Sylvia Kunst (s.kunst{at}kno.umcn.nl)
                                                      1. Radboud University Nijmegen, Netherlands
                                                        1. Minna Manninen (minna.t.manninen{at}uta.fi)
                                                        1. University of Tampere, Finland
                                                          1. Ilmari Pyykko (ilmari.pyykko{at}pshp.fi)
                                                          1. University of Tampere, Finland
                                                            1. Amalia Díaz-Lacava (amalia{at}mail.imsdd.meb.uni-bonn.de)
                                                            1. University of Bonn, Germany
                                                              1. Michael Steffens (steffens{at}mail.imsdd.meb.uni-bonn.de)
                                                              1. University of Bonn, Germany
                                                                1. Thomas Wienker (wienker{at}uni-bonn.de)
                                                                1. University of Bonn, Germany
                                                                  1. Lut Van Laer (lut.vanlaer{at}ua.ac.be)
                                                                  1. University of Antwerp, Belgium

                                                                    Abstract

                                                                    Age-related hearing impairment (ARHI) is the most common sensory impairment in elderly people, affecting 50% of 80 year old people. In the general population, the fraction of elderly is increasing and as a consequence the number of individuals affected with ARHI is growing. ARHI is a complex disorder with both environmental and genetic factors contributing to the disease. Recently, the first studies to elucidate these genetic factors have been performed, resulting in the identification of the first two susceptibility genes for ARHI, NAT2 and KCNQ4. Within the current study, the association between ARHI and polymorphisms in genes that contribute to the defence against Reactive Oxygen Species (ROS), including GSTT1, GSTM1 and NAT2, was tested. Samples originated from 7 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, gene-environment and gene-gene interactions. We detected an association between ARHI and GSTT1 and GSTM1 in the Finnish population sample, as well as NAT2*6A in the general European population sample. This latter finding replicates previously published data. As in the study of complex disorders replication is considered the ultimate proof of true associations, the current study provides further support for the involvement of NAT2*6A in ARHI.

                                                                    • Age related Hearing Impairment
                                                                    • Association study
                                                                    • Glutathione S transferase
                                                                    • N-acetyltransferase
                                                                    • ROS

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