Journal article

Exome sequencing in HFE C282Y homozygous men with extreme phenotypes identifies a GNPAT variant associated with severe iron overload

Christine E McLaren, Mary J Emond, V Nathan Subramaniam, Pradyumna D Phatak, James C Barton, Paul C Adams, Justin B Goh, Cameron J McDonald, Lawrie W Powell, Lyle C Gurrin, Katrina J Allen, Deborah A Nickerson, Tin Louie, Grant A Ramm, Gregory J Anderson, Gordon D McLaren

Hepatology | WILEY | Published : 2015


UNLABELLED: To identify polymorphisms associated with variability of iron overload severity in HFE-associated hemochromatosis, we performed exome sequencing of DNA from 35 male HFE C282Y homozygotes with either markedly increased iron stores (n = 22; cases) or with normal or mildly increased iron stores (n = 13; controls). The 35 participants, residents of the United States, Canada, and Australia, reported no or light alcohol consumption. Sequencing data included 82,068 single-nucleotide variants, and 10,337 genes were tested for a difference between cases and controls. A variant in the GNPAT gene showed the most significant association with severe iron overload (P = 3 × 10(-6) ; P = 0.033 b..

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