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Human Estrogen Receptor ß 548 Is Not a Common Variant in Three Distinct Populations

Karolinska Institute (L.X., Q.P.-H., A.F., K.H., L.H., J.-Å.G., K.D.-W.), Department of Biosciences at Novum, SE-14157 Huddinge, Sweden; Centre de Recherche (D.L.), Hôpital Sainte-Justine, Département de Pédiatrie, Université de Montréal, Québec, Canada H3T 1C5; and Division of Molecular Genetic Epidemiology (K.H.), German Cancer Research Center, Heidelberg D-69120, Germany

Address all correspondence and requests for reprints to: Karin Dahlman-Wright, Center for Biotechnology, Novum, Karolinska Institute, SE-141 57 Huddinge, Sweden. E-mail: kada{at}cbt.ki.se

Several isoforms of estrogen receptor (ER) ß (also known as NR3A2) have been reported, including variants with different N-terminal ends. In rodents, two in-frame initiation codons (ATGs) are used to produce proteins of 530 and 549 amino acids, respectively. In humans, the upstream ATG is out of frame in all clones reported, until recently, when human clones with an extra A-T base pair placing the upstream ATG in frame were reported. The authors suggested that this could represent a novel polymorphism in the ERß gene. Because human ERß548 (hERß548) and hERß530 display different functional characteristics in vitro, it is of interest to determine if this variant constitutes a polymorphism in human populations. We therefore determined the frequency of this novel isoform in several populations including African (n = 96), Caucasian (n = 100), and Asian (n = 128) subjects using denaturing HPLC. We did not detect any alleles that correspond to hERß548 in these samples or in additional samples of heterogeneous origin. It is concluded that hERß548 is not a common variant in Africans, Caucasians, or Asians.

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