LETTERS TO THE EDITOR
nature publishing group
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risk in males. In any case, we believe that gender must be considered in the risk evaluation due to the female predominance in celiac disease. REFERENCES 1. Megiorni F, Mora B, Bonamico M et al. HLADQ and susceptibility to celiac disease: evidence for gender differences and parent-of-origin effects. Am J Gastroenterol 2008;103:997–1003. 2. Hunt KA, Zhernakova A, Turner G et al. Newly identified genetic risk variants for celiac disease related to the immune response. Nat Genet 2008;40:395–402. 3. Zandman-Goddard G, Peeva E, Shoenfeld Y. Gender and autoimmunity. Autoimmun Rev 2007;6:366–72. 4. Holopainen P, Mustalahti K, Uimari P et al. Candidate gene regions and genetic heterogeneity in gluten sensitivity. Gut 2001;48:696–701.
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Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy; 2 Department of Pediatrics, “Sapienza” University of Rome, Rome, Italy. Correspondence: Maria Cristina Mazzilli, BSc, Department of Experimental Medicine, “Sapienza” University of Rome, Viale Regina Elena, Rome 324-00161, Italy. E-mail:
[email protected].
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To the Editor: Concern has been raised from Dubois et al. about our observation of an increased frequency of HLA DQ2/ DQ8-positive females with celiac disease (CD) compared with males (94.3% vs. 85.2%, P = 1.6×10 − 3) (1). The resulting ORs were 40.5 and 14.1, respectively in the two genders, suggesting that the presence of at least one of the two dimers is a risk factor stronger in females than in males. These data were obtained in a cohort of Italian affected children and were not confirmed by Hunt et al. (2) in adult celiac individuals from the United Kingdom. Dubois et al. asserts that our results could be due to a type 1 error, however it should be taken into con-
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doi: 0.1038/ajg.2009.19
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Francesca Megiorni, BSc1, Barbara Mora, BSc1, Margherita Bonamico, MD2, Maria Barbato, MD2, Monica Montuori, MD2, Franca Viola, MD2, Simonetta Trabace, BSc1 and Maria Cristina Mazzilli, BSc1
sideration that the two studies analyze patients with different ages at disease onset and belonging to diverse populations. Further studies in various ethnic groups are needed to define the relationship between gender and HLA-dependent CD susceptibility. Several articles discuss the impact of gender in the pathogenesis of autoimmune diseases that may be related to sex hormones and/or sex-related genes (3). Holopainen et al. (4) showed stronger evidence of genetic linkage in three non-HLA candidate regions (5q, 11q and 2q33) in families with affected males, speculating that HLA-DQ is a risk factor for both sexes but non-HLA risk factors play a major role in males compared with females. With regard to the comment on excess of DQ2.5cis homozygotes in females, we wish to emphasize that Figure 1 shows the female to male ratio rather than the allele frequencies in the two sexes. Indeed, the reported 1.67 ratio is lower than the 1.8 value found in the whole cohort and we stated in the article that the occurrence of two DQB1 susceptible alleles seemed to increase the disease
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Response to Dr Dubois et al.
© 2009 by the American College of Gastroenterology
The American Journal of GASTROENTEROLOGY
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