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Genetic and environmental factors associated with vitamin B12 status in Amazonian children

  • Fernanda Cobayashi (a1), Luciana Yuki Tomita (a2), Rosangela Aparecida Augusto (a1), Vania D’Almeida (a3) and Marly Augusto Cardoso (a1)...

Abstract

Objective

To evaluate the prevalence of vitamin B12 deficiency and factors associated with vitamin B12 status in Amazonian children.

Design

Genetic risk score (GRS), socio-economic and nutritional status, and morbidity data were the independent variables used in multiple linear regression models to evaluate factors associated with vitamin B12 status in a population-based cross-sectional study. GRS was created by summing a number of known risk alleles for low serum vitamin B12.

Setting

Acrelândia, western Brazilian Amazon.

Subjects

Children (n 988) aged <10 years.

Results

Overall prevalence of vitamin B12 deficiency (<150 pmol/l) was 4·2 (95 % CI 3·0, 5·6) % and was highest in children aged <24 months: 13·6 (95 % CI % 8·8, 19·7) %. For children <24 months, wealth index (β=0·017, P=0·030) and animal protein intake =0·219, P=0·003) were positively associated with vitamin B12 status. GRS (β=−0·114, P<0·001) and serum homocysteine (β=–0·049, P<0·001) were negatively associated. Among children aged ≥24 months, vitamin B12 status was positively associated with wealth index (β=0·012, P<0·001), height-for-age Z-score (β=0·024, P=0·033) and serum vitamin A (β=0·089, P<0·001). Age≥60 months =–0·118, P<0·001), GRS (β=–0·048, P<0·001), maternal schooling <5 years (β=–0·083, P<0·001), low intake of animal-derived foods (β=–0·050, P=0·030), serum homocysteine (β=–0·053, P<0·001), serum folate ≥23·6 nmol/l (β=–0·055, P=0·012) and geohelminth infection (β=–0·141, P=0·017) were negatively associated with vitamin B12 status.

Conclusions

GRS, poverty, low intake of animal-derived foods, geohelminth infection, vitamin A and folate status were important factors associated with vitamin B12 status of children in our study.

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Copyright

Corresponding author

*Corresponding author: Email marlyac@usp.br

Footnotes

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See Appendix for full list of members of the ACTION Study Team.

Footnotes

References

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1. Stabler, SP (2013) Vitamin B12 deficiency. N Engl J Med 368, 20412042.
2. Honzik, T, Adamovicova, M, Smolka, V et al. (2010) Clinical presentation and metabolic consequences in 40 breastfed infants with nutritional vitamin B12 deficiency – what have we learned? Eur J Paediatr Neurol 14, 488495.
3. Bjørke-Monsen, AL & Ueland, PM (2011) Cobalamin status in children. J Inherit Metab 34, 111119.
4. Strand, TA, Taneja, S, Ueland, PM et al. (2013) Cobalamin and folate status predicts mental development scores in North Indian children 12–18 mo of age. Am J Clin Nutr 97, 310317.
5. Demir, N, Kok, A, Ustyol, L et al. (2013) Clinical and neurological findings of severe vitamin B12 deficiency in infancy and importance of early diagnosis and treatment. J Paediatr Child Health 49, 820824.
6. McLean, ED, Allen, LH, Neumann, CG et al. (2007) Low plasma vitamin B-12 in Kenyan school children is highly prevalent and improved by supplemental animal source foods. J Nutr 137, 676682.
7. Pawlak, R, Parrott, SJ, Raj, S et al. (2013) How prevalent is vitamin B12 deficiency among vegetarians? Nutr Rev 71, 110117.
8. Villamor, E, Mora-Plazas, M, Forero, Y et al. (2008) Vitamin B-12 status is associated with socioeconomic level and adherence to an animal food dietary pattern in Colombian school children. J Nutr 138, 13911398.
9. Allen, LH (2008) Causes of vitamin B12 and folate deficiency. Food Nutr Bull 29, Suppl. 2, S20S34.
10. Tancer-Elci, H, Isik-Balcu, Y, Bor-Kucukatay, M et al. (2014) Investigation of hemorheological parameters at the diagnosis and the follow up of nutritional vitamin B12 deficient children. Clin Hemorheol Microcirc (Epublication ahead of print version).
11. Rasmussen, SA, Fernhoff, PM & Scanlon, KS (2001) Vitamin B12 deficiency in children and adolescents. J Pediatr 138, 1017.
12. Cuevas-Nasu, L, Mundo-Rosas, V, Shamah-Levy, T et al. (2012) Prevalence of folate and vitamin B12 deficiency in Mexican children aged 1 to 6 years in a population-based survey. Salud Publica Mex 54, 116124.
13. Jones, KM, Ramirez-Zea, M, Zuleta, C et al. (2007) Prevalent vitamin B-12 deficiency in twelve-month-old Guatemalan infants is predicted by maternal B-12 deficiency and infant diet. J Nutr 137, 13071313.
14. Haggarty, P (2007) B-vitamins, genotype and disease causality. Proc Nutr Soc 66, 539547.
15. Tanaka, T, Scheet, P, Giusti, B et al. (2009) Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations. Am J Hum Genet 84, 477482.
16. Hazra, A, Kraft, P, Selhub, J et al. (2008) Common variants of FUT2 are associated with plasma vitamin B12 levels. Nat Genet 40, 11601162.
17. Hazra, A, Kraft, P, Lazarus, R et al. (2009) Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway. Hum Mol Genet 18, 46774687.
18. Tanwar, VS, Chand, MP, Kumar, J et al. (2013) Common variant in FUT2 gene is associated with levels of vitamin B12 in Indian population. Gene 515, 224228.
19. Bailey, LB & Gregory, JF (1999) Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirement. J Nutr 129, 919922.
20. Frosst, P, Blom, HJ, Milos, R et al. (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10, 111113.
21. Palladino, M, Chiusolo, P, Reddiconto, G et al. (2009) MTHFR polymorphisms involved in vitamin B12 deficiency associated with atrophic gastritis. Biochem Genet 47, 645650.
22. Thuesen, BH, Husemoen, LL, Ovesen, L et al. (2010) Lifestyle and genetic determinants of folate and vitamin B12 levels in a general adult population. Br J Nutr 103, 11951204.
23. Ozarda, Y, Sucu, DK, Hizli, B et al. (2009) Rate of T alleles and TT genotype at MTHFR 677C→T locus or C alleles and CC genotype at MTHFR 1298A→C locus among healthy subjects in Turkey: impact on homocysteine and folic acid status and reference intervals. Cell Biochem Funct 27, 568577.
24. Cardoso, MA, Scopel, KK, Muniz, PT et al. (2012) Underlying factors associated with anemia in Amazonian children: a population-based, cross-sectional study. PLoS One 7, e36341.
25. Travassos, C & Williams, DR (2004) The concept and measurement of race and their relationship to public health: a review focused on Brazil and the United States. Cad Saude Publica 20, 660678.
26. Lohman, TG, Roche, AF & Martorell, R (1988) Anthropometric Standardization Reference Manual. Champaign, IL: Human Kinetics Books.
27. WHO Multicentre Growth Reference Study Group (2006) WHO child growth standards based on length/height, weight and age. Acta Paediatr Suppl 450, 7685.
28. de Onis, M & Lobstein, T (2010) Defining obesity risk status in the general childhood population: which cut-offs should we use? Int J Pediatr Obes 5, 458460.
29. Garcia, MT, Granado, FS & Cardoso, MA (2011) Complementary feeding and nutritional status of 6–24-month-old children in Acrelândia, Acre State, Western Brazilian Amazon. Cad Saude Publica 27, 305316.
30. Scagliusi, FB, Garcia, MT, Indiani, AL et al. (2011) Relative validity of a food-frequency questionnaire developed to assess food intake of schoolchildren living in the Brazilian Western Amazon. Cad Saude Publica 27, 21972206.
31. World Health Organization (2008) Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies. Food Nutr Bull 29, Suppl. 1, S238S244.
32. Gomes, LF, Alves, AF, Sevanian, A et al. (2004) Role of β2-glycoprotein I, LDL-, and antioxidant concentrations in hypercholesterolemic elderly subjects. Antioxid Redox Signal 6, 237244.
33. World Health Organization (2009) Global Prevalence of Vitamin A Deficiency in Populations at Risk 1995–2005. WHO Global Database on Vitamin A Deficiency. Geneva: WHO.
34. World Health Organization (2007) Assessing the Iron Status of Populations, 2nd ed. Geneva: WHO.
35. Thurnham, DI, McCabe, LD, Haldar, S et al. (2010) Adjusting plasma ferritin concentrations to remove the effects of subclinical inflammation in the assessment of iron deficiency: a meta-analysis. Am J Clin Nutr 92, 546555.
36. Hoffman, WA, Pons, JA & Janer, JL (1934) The sedimentation concentration method in Schistosomiasis mansoni . Puerto Rico J Public Health Trop Med 9, 283298.
37. Myakishev, MV, Khripin, Y, Hu, S et al. (2001) High-throughput SNP genotyping by allele-specific PCR with universal energy-transfer-labeled primers. Genome Res 11, 163169.
38. Rusch, TL, Dickinson, W, Che, J et al. (2003) Instrumentation for continuous array genotyping of short insert/deletion polymorphisms. Proceedings of the SPIE – Microarrays and Combinatorial Technologies for Biomedical Applications: Design, Fabrication, and Analysis 4966, 138145.
39. Filmer, D & Pritchett, LH (2001) Estimating wealth effects without expenditure data – or tears: an application to educational enrolments in states of India. Demography 38, 115132.
40. García-Casal, MN, Osorio, C, Landaeta, M et al. (2005) High prevalence of folic acid and vitamin B12 deficiencies in infants, children, adolescents and pregnant women in Venezuela. Eur J Clin Nutr 59, 10641070.
41. Osei, A, Houser, R & Bulusu, S (2010) Nutritional status of primary schoolchildren in Garhwali Himalayan villages of India. Food Nutr Bull 31, 221233.
42. Allen, LH (2012) Adequacy of family foods for complementary feeding. Am J Clin Nutr 95, 785786.
43. Allen, LH (2012) B vitamins in breast milk: relative importance of maternal status and intake, and effects on infant status and function. Adv Nutr 3, 362369.
44. Huemer, M, Vonblon, K, Födinger, M et al. (2006) Total homocysteine, folate, and cobalamin, and their relation to genetic polymorphisms, lifestyle and body mass index in healthy children and adolescents. Pediatr Res 60, 764769.
45. Kelly, RJ, Rouquier, S, Giorgi, D et al. (1995) Sequence and expression of a candidate for the human Secretor blood group α(1,2)fucosyltransferase gene (FUT2). Homozygosity for an enzyme-inactivating nonsense mutation commonly correlates with the non-secretor phenotype. J Biol Chem 270, 46404649.
46. Carmel, R, Aurangzeb, I & Qian, D (2001) Associations of food-cobalamin malabsorption with ethnic origin, age, Helicobacter pylori infection, and serum markers of gastritis. Am J Gastroenterol 96, 6370.
47. Oussalah, A, Besseau, C, Chery, C et al. (2012) Helicobacter pylori serologic status has no influence on the association between fucosyltransferase 2 polymorphism (FUT2 461 G→A) and vitamin B-12 in Europe and West Africa. Am J Clin Nutr 95, 514521.
48. Chery, C, Hehn, A, Mrabet, N et al. (2013) Gastric intrinsic factor deficiency with combined GIF heterozygous mutations and FUT2 secretor variant. Biochimie 95, 9951001.
49. Hanumante, NM, Wadia, RS, Deshpande, SS et al. (2008) Vitamin B12 and homocysteine status in asymptomatic Indian toddlers. Indian J Pediatr 75, 751753.
50. Ueland, PM & Monsen, AL (2003) Hyperhomocysteinemia and B-vitamin deficiencies in infants and children. Clin Chem Lab Med 41, 14181426.
51. Carmel, R, Green, R & Rosenblatt, DS (2003) Update on cobalamin, folate, and homocysteine. Hematology Am Soc Hematol Educ Program 1, 6281.
52. Institute of Medicine (2001) Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium and Zinc. Washington, DC: National Academy Press.
53. Tanumihardjo, SA (2011) Vitamin A: biomarkers of nutrition for development. Am J Clin Nutr 94, Suppl. 1, S658S665.
54. Lopez-Teros, V, Quihui-Cota, L & Méndez-Estrada, RO (2013) Vitamin A-fortified milk increases total body vitamin A stores in Mexican preschoolers. J Nutr 143, 221226.

Keywords

Genetic and environmental factors associated with vitamin B12 status in Amazonian children

  • Fernanda Cobayashi (a1), Luciana Yuki Tomita (a2), Rosangela Aparecida Augusto (a1), Vania D’Almeida (a3) and Marly Augusto Cardoso (a1)...

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