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Aspects physiopathologiques et moléculaires des causes gastriques de la malabsorption en vitamine B12

Abstract : There are multiple causes of gastric vitamin B12 malabsorption. To get a better understanding of their physiopathology, we are interested in inherited gastric intrinsic factor (GIF) deficiency, a vitamin B12 absorption defect characterized by GIF impaired activity. In this study, we report five cases heterozygous carriers of the variant GIF c.290T>C (p.M97T) and two cases heterozygous carriers of the variant GIF c.435_437delGAA (p.K145_N146delinsN). The study of recombinant mutated GIF produced by site-directed mutagenesis evidenced a reduced affinity for vitamin B12 in the case of GIF p.K145_N146delinsN which does not explain fully the phenotypes observed in our subjects. Recently, an association was described between the FUT2 polymorphism rs601338, c.461 G>A, coding for a fucosyltransferase, and plasma levels of vitamin B12. To complete our study, we assessed the influence of FUT2 c.461 G>A polymorphism on vitamin B12, folate and homocysteine in European and African populations in 1466 subjects. Our study demonstrate a clear effect of FUT2 c.461 G>A polymorphism on both plasma levels of vitamin B12 and folate, regardless of age, gender, and geographic origin. In conclusion, our results demonstrate the GIF gene is not the only gene involved in the physiopathology of inherited GIF deficiency. It is necessary to study the gastric causes of vitamin B12 malabsorption through a polygenic approach, in which the FUT2 gene is an important element
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http://docnum.univ-lorraine.fr/prive/SCD_T_2011_0126_BESSEAU.pdf
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https://hal.univ-lorraine.fr/tel-01746290
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Submitted on : Thursday, March 29, 2018 - 10:30:13 AM
Last modification on : Tuesday, October 13, 2020 - 10:46:28 AM

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  • HAL Id : tel-01746290, version 1

Citation

Cyril Besseau. Aspects physiopathologiques et moléculaires des causes gastriques de la malabsorption en vitamine B12. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2011. Français. ⟨NNT : 2011NAN10126⟩. ⟨tel-01746290⟩

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