Skip to main content
SpringerLink
Log in

Polymorphisms of haptoglobin modify the relationship between dietary iron and the risk of gestational iron-deficiency anemia

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

To assess whether polymorphisms of haptoglobin (Hp) modify the relationship between dietary iron and the risk of gestational iron-deficiency anemia (IDA).

Methods

This study analyzed 1430 singleton pregnant women aged 20 ~ ≤ 48 years from the 2017–2019 National Nutrition and Health Survey of Pregnant Women in Taiwan. Sociodemographic, blood biochemical, Hp phenotype, and 24-h dietary recall data were collected. Erythropoiesis-related total prenatal supplementation was defined as the reported use of multivitamins and minerals, vitamin B complex, folate, and iron.

Results

Distributions of the Hp 1-1, Hp 2-1, and Hp 2-2 phenotypes were 13.6, 39.8, and 46.5%, respectively. Women with the Hp 1-1 phenotype had the lowest mean levels of serum ferritin (p-trend = 0.017), the highest prevalence of gestational ID (p-trend = 0.033) as well as the highest prevalence of gestational IDA (did not reach statistical differences, p-trend = 0.086). A gene–diet interaction on serum ferritin was observed between the Hp 1 and Hp 2 (2-1/2-2) alleles (p < 0.001). An adjusted multivariate logistic regression showed that compared to those with a normal blood iron status and who reported using erythropoiesis-related total prenatal supplements, those who did not had a 4.05-fold [odds ratio (OR) = 4.05 (95% confidence interval (CI) 2.63–6.24), p < 0.001] increased risk of gestational IDA. The corresponding ORs for carriers of the Hp 1 and Hp 2 alleles were 4.78 (95% CI 1.43–15.99) and 3.79 (95% CI 2.37–6.06), respectively.

Conclusion

Pregnant women who are Hp 1 carriers are at increased risk for developing IDA if they do not meet the recommended dietary allowance for iron or use erythropoiesis-related prenatal supplements.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Availability of data and materials

Data described in the manuscript, code book, and analytic code will be made available from the corresponding author on reasonable request.

Abbreviations

ANOVA:

Analysis of variance

CD163:

Cluster of differentiation 163

DRI:

Dietary reference intake

Hb:

Hemoglobin

Hp:

Haptoglobin

ID:

Iron deficiency

IDA:

Iron-deficiency anemia

NAHSIT:

Nutrition and Health Survey in Taiwan

NTD:

New Taiwan Dollar

pBMI:

Pre-pregnancy body mass index

pBW:

Pre-pregnancy body weight

RDAs:

Recommended Dietary Allowances

SD:

Standard deviation

SF:

Serum ferritin

TS:

Transferrin saturation

References

  1. Teichman J, Nisenbaum R, Lausman A, Sholzberg M (2021) Suboptimal iron deficiency screening in pregnancy and the impact of socioeconomic status in a high-resource setting. Blood Adv 5(22):4666–4673. https://doi.org/10.1182/bloodadvances.2021004352

    Article  CAS  Google Scholar 

  2. Fisher AL, Nemeth E (2017) Iron homeostasis during pregnancy. Am J Clin Nutr 106(Suppl 6):1567S-1574S. https://doi.org/10.3945/ajcn.117.155812

    Article  Google Scholar 

  3. Sangkhae V, Fisher AL, Wong S, Koenig MD, Tussing-Humphreys L, Chu A, Lelić M, Ganz T, Nemeth E (2021) Effects of maternal iron status on placental and fetal iron homeostasis. J Clin Investig. https://doi.org/10.1172/JCI127341

    Article  Google Scholar 

  4. Stoffel NU, Zimmermann MB, Cepeda-Lopez AC, Cervantes-Gracia K, Llanas-Cornejo D, Zeder C, Tuntipopipat S, Moungmaithong S, Densupsoontorn N, Quack-Loetscher K, Gowachirapant S, Herter-Aeberli I (2021) Maternal iron kinetics and maternal-fetal iron transfer in normal weight and overweight pregnancy. Am J Clin Nutr. https://doi.org/10.1093/ajcn/nqab406

    Article  Google Scholar 

  5. World Health Organization (2015) The global prevalence of anaemia in 2011. WHO Document Production Services, Geneva

    Google Scholar 

  6. World Health Organization (2016) WHO recommendations on antenatal care for a positive pregnancy experience. WHO Document Production Services, Geneva

    Google Scholar 

  7. Milman N, Taylor CL, Merkel J, Brannon PM (2017) Iron status in pregnant women and women of reproductive age in Europe. Am J Clin Nutr 106(suppl 6):1655S-1662S. https://doi.org/10.3945/ajcn.117.156000

    Article  Google Scholar 

  8. Dewey KG, Oaks BM (2017) U-shaped curve for risk associated with maternal hemoglobin, iron status, or iron supplementation. Am J Clin Nutr 106(Suppl 6):1694s–1702s. https://doi.org/10.3945/ajcn.117.156075

    Article  Google Scholar 

  9. Ordovas JM, Ferguson LR, Tai ES, Mathers JC (2018) Personalised nutrition and health. BMJ (Clinical Research ed) 361:bmj2173. https://doi.org/10.1136/bmj.k2173

    Article  Google Scholar 

  10. Cahill LE, Rimm EB (2015) Diet-gene interactions: haptoglobin genotype and nutrient status. In: Bendich A, Deckelbaum RJ (eds) Preventive nutrition: the comprehensive guide for health professionals. Springer, Cham, pp 115–129

    Chapter  Google Scholar 

  11. Andersen CBF, Stodkilde K, Saederup KL, Kuhlee A, Raunser S, Graversen JH, Moestrup SK (2017) Haptoglobin. Antioxid Redox Signal 26(14):814–831. https://doi.org/10.1089/ars.2016.6793

    Article  CAS  Google Scholar 

  12. Langlois MR, Delanghe JR (1996) Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem 42(10):1589–1600

    Article  CAS  Google Scholar 

  13. Delanghe JR, Langlois MR (2002) Haptoglobin polymorphism and body iron stores. Clin Chem Lab Med 40(3):212–216. https://doi.org/10.1515/CCLM.2002.035

    Article  CAS  Google Scholar 

  14. Langlois MR, Martin ME, Boelaert JR, Beaumont C, Taes YE, De Buyzere ML, Bernard DR, Neels HM, Delanghe JR (2000) The haptoglobin 2–2 phenotype affects serum markers of iron status in healthy males. Clin Chem 46(10):1619–1625

    Article  CAS  Google Scholar 

  15. Nyakeriga AM, Troye-Blomberg M (2013) Haptoglobin phenotypes and iron status in children living in a malaria endemic area of Kenyan coast. Acta Trop 126(2):127–131. https://doi.org/10.1016/j.actatropica.2013.02.004

    Article  CAS  Google Scholar 

  16. Kasvosve I, Gordeuk VR, Delanghe JR, Gomo ZA, Gangaidzo IT, Khumalo H, Moyo VM, Saungweme T, Mvundura E, Boelaert JR (2002) Iron status in black persons is not influenced by haptoglobin polymorphism. Clin Chem Lab Med 40(8):810–813. https://doi.org/10.1515/CCLM.2002.140

    Article  CAS  Google Scholar 

  17. Cahill LE, El-Sohemy A (2010) Haptoglobin genotype modifies the association between dietary vitamin C and serum ascorbic acid deficiency. Am J Clin Nutr 92(6):1494–1500. https://doi.org/10.3945/ajcn.2010.29306

    Article  CAS  Google Scholar 

  18. Tang KY, Huang SY, Cheng TM, Bai CH, Chang JS (2020) Haptoglobin phenotype influences the effectiveness of diet-induced weight loss in middle-age abdominally obese women with metabolic abnormalities. Clin Nutr 39(1):225–233. https://doi.org/10.1016/j.clnu.2019.01.019

    Article  CAS  Google Scholar 

  19. Tu SH, Chen C, Hsieh YT, Chang HY, Yeh CJ, Lin YC, Pan WH (2011) Design and sample characteristics of the 2005–2008 Nutrition and Health Survey in Taiwan. Asia Pac J Clin Nutr 20(2):225–237

    Google Scholar 

  20. Hughes RA, Heron J, Sterne JAC, Tilling K (2019) Accounting for missing data in statistical analyses: multiple imputation is not always the answer. Int J Epidemiol 48(4):1294–1304. https://doi.org/10.1093/ije/dyz032

    Article  Google Scholar 

  21. Taiwan Food and Drug Administration Ministry of Health and Welfare (2012) 7th Edition of the Taiwan's Dietary Reference Intakes. Taiwan Food and Drug Administration Ministry of Health and Welfare, Taipei

  22. Health Promotion Administration Ministry of Health and Welfare (2018) Maternal health booklet. Health Promotion Administration Ministry of Health and Welfare, Taipei

  23. World Health Organization (2001) Iron deficiency anaemia: assessment, prevention and control: a guide for programme managers. World Health Organization, Geneva

    Google Scholar 

  24. Centers for Disease Control and Prevention (1998) Recommendations to prevent and control iron deficiency in the United States. MMWR Recomm Rep 47(RR-3):1–29

    Google Scholar 

  25. Chen KJ, Pan WH, Lin YC, Lin BF (2011) Trends in folate status in the Taiwanese population aged 19 years and older from the Nutrition and Health Survey in Taiwan 1993–1996 to 2005–2008. Asia Pac J Clin Nutr 20(2):275–282

    CAS  Google Scholar 

  26. de Benoist B (2008) Conclusions of a WHO technical consultation on folate and vitamin B12 deficiencies. Food Nutr Bull 29(2 Suppl):S238-244. https://doi.org/10.1177/15648265080292S129

    Article  Google Scholar 

  27. Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SK, Moestrup SK (2001) Identification of the haemoglobin scavenger receptor. Nature 409(6817):198–201. https://doi.org/10.1038/35051594

    Article  CAS  Google Scholar 

  28. Slusarczyk P, Mleczko-Sanecka K (2021) The multiple facets of iron recycling. Genes 12(9):1364. https://doi.org/10.3390/genes12091364

    Article  CAS  Google Scholar 

  29. Chang TY, Liu KL, Chang CS, Su CT, Chen SH, Lee YC, Chang JS (2018) Ferric citrate supplementation reduces red-blood-cell aggregation and improves CD163+ macrophage-mediated hemoglobin metabolism in a rat model of high-fat-diet-induced obesity. Mol Nutr Food Res. https://doi.org/10.1002/mnfr.201700442

    Article  Google Scholar 

  30. Semba RD, Bloem MW (2002) The anemia of vitamin A deficiency: epidemiology and pathogenesis. Eur J Clin Nutr 56(4):271–281. https://doi.org/10.1038/sj.ejcn.1601320

    Article  CAS  Google Scholar 

  31. Dreyfuss ML, Stoltzfus RJ, Shrestha JB, Pradhan EK, LeClerq SC, Khatry SK, Shrestha SR, Katz J, Albonico M, West KP Jr (2000) Hookworms, malaria and vitamin A deficiency contribute to anemia and iron deficiency among pregnant women in the plains of Nepal. J Nutr 130(10):2527–2536. https://doi.org/10.1093/jn/130.10.2527

    Article  CAS  Google Scholar 

  32. da Cunha MSB, Campos Hankins NA, Arruda SF (2019) Effect of vitamin A supplementation on iron status in humans: A systematic review and meta-analysis. Crit Rev Food Sci Nutr 59(11):1767–1781. https://doi.org/10.1080/10408398.2018.1427552

    Article  CAS  Google Scholar 

  33. Mendes JF, Siqueira EM, de Brito ESJG, Arruda SF (2016) Vitamin A deficiency modulates iron metabolism independent of hemojuvelin (Hfe2) and bone morphogenetic protein 6 (Bmp6) transcript levels. Genes Nutr 11:1. https://doi.org/10.1186/s12263-016-0519-4

    Article  CAS  Google Scholar 

  34. Paciolla C, Fortunato S, Dipierro N, Paradiso A, De Leonardis S, Mastropasqua L, de Pinto MC (2019) Vitamin C in plants: from functions to biofortification. Antioxidants (Basel). https://doi.org/10.3390/antiox8110519

    Article  Google Scholar 

  35. Powers JM, Auerbach M (2020) Iron supplementation in infants: a reflection on hepcidin and fractional iron absorption. Am J Clin Nutr 112(4):909–910. https://doi.org/10.1093/ajcn/nqaa224

    Article  Google Scholar 

  36. Milman NT (2021) Managing genetic hemochromatosis: an overview of dietary measures, which may reduce intestinal iron absorption in persons with iron overload. Gastroenterol Res 14(2):66–80. https://doi.org/10.14740/gr1366

    Article  CAS  Google Scholar 

  37. Wobeto VPdA, Zaccariotto TR, Sonati MdF (2008) Polymorphism of human haptoglobin and its clinical importance. Genet Mol Biol 31(3):602–620

    Article  CAS  Google Scholar 

  38. Zhao H, Zhang G, Duan Y, Yu S (1993) Haptoglobin types in Chinese ethnic groups. Hum Hered 43(2):131–133. https://doi.org/10.1159/000154130

    Article  CAS  Google Scholar 

  39. Asleh R, Briasoulis A, Berinstein EM, Wiener JB, Palla M, Kushwaha SS, Levy AP (2018) Meta-analysis of the association of the haptoglobin genotype with cardiovascular outcomes and the pharmacogenomic interactions with vitamin E supplementation. Pharmacogenom Personal Med 11:71–82. https://doi.org/10.2147/PGPM.S159454

    Article  CAS  Google Scholar 

  40. Mayasari NR, Hu TY, Chao JC, Bai CH, Chen YC, Huang YL, Chang CC, Wang FF, Hadi H, Nurwanti E, Chang JS (2021) Associations of the pre-pregnancy weight status with anaemia and the erythropoiesis-related micronutrient status. Public Health Nutr 24(18):6247–6257. https://doi.org/10.1017/s1368980021002627

    Article  Google Scholar 

Download references

Acknowledgements

All the authors would like to thank the Ministry of Health and Welfare, Taiwan for allowing us to retrieve data of the NAHSIT-PW 2017–2019.

Funding

Dr. Jung-Su Chang was supported by grants from Taipei Medical University Hospital [111TMU-TMUH-054] and the Ministry of Science and Technology, Taiwan [MOST109-2923-B-038-001-MY3 and MOST 111-2320-B-038-030-MY3].

Author information

Author notes

  1. Tzu-Yu Hu and Noor Rohmah Mayasari have contributed equally to this work.

Authors and Affiliations

  1. School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, 250 Wu-Xing Street, Taipei, 11031, Taiwan

    Tzu-Yu Hu, Noor Rohmah Mayasari, Jane C.-J. Chao & Jung-Su Chang

  2. Graduate Institute of Translational Medicine, College of Medical Sciences and Technology, Taipei Medical University, Taipei, Taiwan

    Tsai-Mu Cheng

  3. Department of Public Health, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Chyi-Huey Bai & Ya-Li Huang

  4. Department of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan

    Chyi-Huey Bai & Ya-Li Huang

  5. College of Public Health, Master Program in Global Health and Development, Taipei Medical University, Taipei, Taiwan

    Jane C.-J. Chao

  6. Nutrition Research Center, Taipei Medical University Hospital, Taipei, Taiwan

    Jane C.-J. Chao & Jung-Su Chang

  7. Department of Medicine, Yangming Branch, Taipei City Hospital, Taipei, Taiwan

    Fan-Fen Wang

  8. National Yang-Ming University School of Medicine, Taipei, Taiwan

    Fan-Fen Wang

  9. IM Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia

    Anatoly V. Skalny & Alexey A. Tinkov

  10. KG Razumovsky Moscow State University of Technologies and Management, 109004, Moscow, Russia

    Anatoly V. Skalny

  11. Yaroslavl State University, Yaroslavl, Russia

    Alexey A. Tinkov

  12. Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan

    Jung-Su Chang

  13. Chinese Taipei Society for the Study of Obesity (CTSSO), Taipei, Taiwan

    Jung-Su Chang

Authors
  1. Tzu-Yu Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Noor Rohmah Mayasari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tsai-Mu Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chyi-Huey Bai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jane C.-J. Chao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ya-Li Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fan-Fen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anatoly V. Skalny
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alexey A. Tinkov
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jung-Su Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JSC conceived and designed the research; TYH, CHB, and JCC conducted the research; TMC, YLH, and FFW provided the materials; TYH and NRM performed the statistical analyses; TYH, NRM, and JSC wrote the manuscript; JSC had primary responsibility for the final content; and all the authors read and approved the final manuscript.

Corresponding author

Correspondence to Jung-Su Chang.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Ethics approval

This study was approved by the Taipei Medical University Institutional Review Board (TMU-JIRB N201707039) (https://ohr.tmu.edu.tw).

Supplementary Information

Below is the link to the electronic supplementary material.

Fig S1.

Flow chart of the study participants

Supplementary file1 (DOCX 1155 KB)

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hu, TY., Mayasari, N.R., Cheng, TM. et al. Polymorphisms of haptoglobin modify the relationship between dietary iron and the risk of gestational iron-deficiency anemia. Eur J Nutr 62, 299–309 (2023). https://doi.org/10.1007/s00394-022-02987-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-022-02987-9

Keywords

Search

Navigation