Role of (Glu → Arg, Q5R) mutation of the intrinsic factor in pernicious anemia and other causes of low vitamin B12

Dear Editor, Pernicious anemia is a vitamin B12 deficiency caused by a lack of gastric intrinsic factor due to an autoimmune chronic atrophic gastritis. Pernicious anemia is typically an adult disease unlike congenital intrinsic factor deficiency, which is also known as juvenile or congenital pernicious anemia (online Mendelian inheritance in man (OMIM) accession no. 261000) [1]. The intrinsic factor gene was identified and characterized more than a decade ago [2, 3]. As a consequence, a number of abnormalities in the intrinsic factor gene were found in patients with congenital intrinsic factor deficiency [4–6]. Moreover, a prevalent polymorphism in the intrinsic factor gene was observed, in which glutamic acid was replaced by an arginin in position 5 (Glu→Arg, Q5R) [4, 6]. Apparently, this mutation does not affect intrinsic factor secretion in vitro [4]. However, a possible role of this mutation in ileal vitamin B12 absorption has not been evaluated. Some patients with congenital intrinsic factor deficiency were homozygous for this mutation [4]; however, recently, the same homozygous mutation has been described in healthy subjects [6]. In the same work, the authors suggested that the Q5R mutation of the intrinsic factor gene is not the cause of the congenital intrinsic factor deficiency [6]. However, interestingly, the authors indicated that this polymorphism could play a role in the development of pernicious anemia in adults [6]. The aim of this work was to evaluate a possible role of the Q5R mutation in the intrinsic factor gene in patients with low vitamin B12 due to pernicious anemia or other causes. In this regard, we studied the mutation in the intrinsic factor gene in 109 patients with pernicious anemia, 36 with other low vitamin B12 disorders, and 273 adult controls. The methodology used in this study has previously been reported [4]. A chi-square test was employed to compare the frequencies between groups using the Statistical Package for the Social Sciences 14.0. DNA results were obtained from 107 out of 109 patients with pernicious anemia, from all cases with other causes of low serum vitamin B12, and from 272 out of 273 controls. In pernicious anemia, seven patients were heterozygous for the Q5R mutation (population frequency 6.5%, allelic frequency 3.25%). In other cases with low vitamin B12, three patients were heterozygous for the mutation (population frequency 8.7%, allelic frequency 4.35%). Furthermore, considering all cases with low vitamin B12 (pernicious anemia plus other cases), 7% of low vitamin B12 cases were heterozygous (allelic frequency 3.5%). Finally, in the control group, six individuals were heterozygous for the same mutation (population frequency 2.2%, allelic frequency 1.1%). Comparing frequencies between the three groups, chisquare test was significant (chi-square 6.028, p=0.049). However, frequencies between pernicious anemia and other causes of low vitamin B12 were not different (Fisher’s exact Ann Hematol (2008) 87:599–600 DOI 10.1007/s00277-008-0465-0