title: MTHFR 677T is a strong determinant of the degree of hearing loss among Polish males with postlingual sensorineural hearing impairment.
abstract: Hearing impairment (HI) is the most common sensory handicap. Congenital HI often has a genetic basis, whereas the etiology of nonsyndromic postlingual HI (npHI) usually remains unidentified. Our purpose was to test whether the MTHFR C677T (rs1801133) polymorphism affecting folate metabolism is associated with the occurrence or severity of npHI. We studied rs1801133 genotypes in 647 npHI patients (age <40, sudden sensorineural loss excluded, HI characterized as mean of better ear hearing thresholds for 0.5-8 kHz) and 3273 adult controls from the background population. Genotype distribution among patients and controls was similar, but among male cases (n = 302) we found a dose-dependent correlation of MTHFR 677T with the degree of HI (mean thresholds in dB: 38.8, 44.9, and 53.3, for CC, CT, and TT genotypes, respectively; p = 0.0013, p(cor.) = 0.017). Among male patients rs1801133 TT significantly increased the risk of severe/profound HI (odds ratio = 4.88, p = 0.001). Among controls the known effect of MTHFR 677T on plasma total homocysteine was more pronounced in men than in women (p<0.00004 for genotype-sex interaction) suggesting that in Poland folate deficiency is more prevalent in males. In conclusion, we report a novel strong effect of MTHFR 677T among males with npHI. The functional significance of rs1801133 suggests that these patients may benefit from folate supplementation-an intervention which is simple, cheap, and devoid of side effects.
authors.affiliation: Institute of Physiology and Pathology of Hearing, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Pollak
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Mueller-Malesinska
authors.forename: Urszula
authors.initials: U
authors.lastname: Lechowicz
authors.forename: Agata
authors.initials: A
authors.lastname: Skorka
authors.forename: Lech
authors.initials: L
authors.lastname: Korniszewski
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Sobczyk-Kopciol
authors.forename: Anna
authors.initials: A
authors.lastname: Waskiewicz
authors.forename: Grazyna
authors.initials: G
authors.lastname: Broda
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Iwanicka-Pronicka
authors.forename: Monika
authors.initials: M
authors.lastname: Oldak
authors.forename: Henryk
authors.initials: H
authors.lastname: Skarzynski
authors.forename: Rafał
authors.initials: R
authors.lastname: Płoski
mesh_terms: D000328:Adult; D000368:Aged; D001309:Auditory Threshold; D016022:Case-Control Studies; D003538:Cystamine / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000097:blood / Q000201:enzymology* / Q000235:genetics* / Q000523:psychology; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: C029174:homocystamine; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D003538:Cystamine