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Genetic Variation of Hemoglobin Gene and Its Impact on Disease Severity

Vol. 2 No. 2 (2025): Oktober:

Hayder Fadhil Okab (1), Imad Badr Jasim (2)

(1) Ministry of Health, Thi-Qar Health Directorate, Iraq
(2) 2Collage of Health and Laboratory Technology, National University of Science and Technology, Thi-Qar, Iraq
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Abstract:

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia and associated with severe complications, including neuropathy, nephropathy, and retinopathy. Oxidative stress plays a crucial role in the progression of these complications. Antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) are essential in mitigating oxidative stress; however, their activity is often impaired in diabetic patients. Despite global research on oxidative stress in diabetes, there is limited evidence from Iraq examining the relationship between antioxidant enzyme activity and glycemic control. This study aimed to assess the levels of antioxidant enzymes (SOD, CAT, and GPx) and their association with glycemic indices (fasting blood glucose and HbA1c) in patients with type 2 diabetes mellitus compared to healthy controls. A case-control study including 60 diabetic patients and 30 healthy controls revealed significantly reduced activities of SOD, CAT, and GPx in diabetic patients (p < 0.05). In contrast, fasting blood glucose and HbA1c were significantly elevated in diabetic subjects compared to controls. A negative correlation was observed between antioxidant enzyme activity and glycemic indices, indicating that poor glycemic control exacerbates oxidative stress. This is among the first studies in Iraq to demonstrate the association between impaired antioxidant defense mechanisms and hyperglycemia in type 2 diabetes mellitus. The findings emphasize the importance of monitoring oxidative stress biomarkers alongside glycemic indices to improve management strategies and prevent diabetic complications.


Highlights:



  1. Vitamin D deficiency was prevalent in 62% of patients with type 2 diabetes mellitus.

  2. Low vitamin D levels were significantly associated with poor glycemic control and longer disease duration.

  3. Age, obesity, and limited sun exposure were identified as key risk factors for vitamin D deficiency in diabetic patients.

References

1. M. Frikha, F. Fakhfakh, S. Mseddi, J. Gargouri, L. Ghali, Z. Labiadh, M. Harrabi, T. Souissi, and H. Ayadi, "Hemoglobin beta S haplotype in the Kebili region (southern Tunisia)," Transfusion Clinique et Biologique: Journal de la Societe Francaise de Transfusion Sanguine, vol. 5, no. 2, pp. 166-172, Apr. 1998.

2. S. Menzel and S. L. Thein, "Genetic modifiers of fetal haemoglobin in sickle cell disease," Molecular Diagnosis & Therapy, vol. 23, no. 2, pp. 235-244, Apr. 2019.

3. K. Gardner, T. Fulford, N. Silver, H. Rooks, N. Angelis, M. Allman, S. Nkya, J. Makani, J. Howard, R. Kesse-Adu, and D. C. Rees, "g (HbF): a genetic model of fetal hemoglobin in sickle cell disease," Blood Advances, vol. 2, no. 3, pp. 235-239, Feb. 13, 2018.

4. S. N. Mtatiro, J. Makani, B. Mmbando, S. L. Thein, S. Menzel, and S. E. Cox, "Genetic variants at HbF-modifier loci moderate anemia and leukocytosis in sickle cell disease in Tanzania," American Journal of Hematology, vol. 90, no. 1, pp. E1-E4, Jan. 2015.

5. M. H. Steinberg and P. Sebastiani, "Genetic modifiers of sickle cell disease," American Journal of Hematology, vol. 87, no. 8, pp. 795-803, Aug. 2012.

6. G. R. Serjeant, "Phenotypic variation in sickle cell disease: the role of beta globin haplotype, alpha thalassemia, and fetal hemoglobin in HbSS," Expert Review of Hematology, vol. 15, no. 2, pp. 107-116, Feb. 1, 2022.

7. Q. Ma, D. F. Wyszynski, J. J. Farrell, A. Kutlar, L. A. Farrer, C. T. Baldwin, and M. H. Steinberg, "Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea," The Pharmacogenomics Journal, vol. 7, no. 6, pp. 386-394, Dec. 2007.

8. I. Akinsheye, N. Solovieff, D. Ngo, A. Malek, P. Sebastiani, M. H. Steinberg, and D. H. Chui, "Fetal hemoglobin in sickle cell anemia: molecular characterization of the unusually high fetal hemoglobin phenotype in African Americans," American Journal of Hematology, vol. 87, no. 2, pp. 217, Dec. 3, 2011.

9. Y. Aizawa, W. Mitsuma, T. Ikrar, and S. Komura, "Molecular genetics," Circulation, vol. 115, pp. 361-367, 2007.

10. A. Haj Khelil, S. Denden, N. Leban, H. Daimi, R. Lakhdhar, G. Lefranc, J. Ben Chibani, and P. Perrin, "Hemoglobinopathies in North Africa: a review," Hemoglobin, vol. 34, no. 1, pp. 1-23, Jan. 1, 2010.

11. G. Hardouin, E. Magrin, A. Corsia, M. Cavazzana, A. Miccio, and M. Semeraro, "Sickle cell disease: from genetics to curative approaches," Annual Review of Genomics and Human Genetics, vol. 24, no. 1, pp. 255-275, Aug. 25, 2023.

12. B. P. Yawn and J. John-Sowah, "Management of sickle cell disease: recommendations from the 2014 expert panel report," American Family Physician, vol. 92, no. 12, pp. 1069-1076A, Dec. 15, 2015.

13. D. C. Rees and J. S. Gibson, "Biomarkers in sickle cell disease," British Journal of Haematology, vol. 156, no. 4, pp. 433-445, Feb. 2012.

14. W. A. Arishi, H. A. Alhadrami, and M. Zourob, "Techniques for the detection of sickle cell disease: a review," Micromachines, vol. 12, no. 5, p. 519, May 5, 2021.

15. S. R. Mendez-Marti, C. Zik, A. Alan, H. Wang, and W. B. Ershler, "Sickle Cell Screening in Adults: A Current Review of Point-of-Care Testing," Journal of Hematology, vol. 13, no. 3, p. 53, Jun. 28, 2024.

16. S. R. Mendez-Marti, C. Zik, A. Alan, H. Wang, and W. B. Ershler, "Sickle Cell Screening in Adults: A Current Review of Point-of-Care Testing," Journal of Hematology, vol. 13, no. 3, p. 53, Jun. 28, 2024.

17. E. I. Obeagu, "Influence of Hemoglobin Variants on Vaso-Occlusive Phenomena in Sickle Cell Anemia: A Review," International Journal of Medical Sciences and Pharma Research, vol. 10, no. 2, pp. 54-59, Jul. 15, 2024.

18. G. Aniyathodiyil and S. Chopra, "Emergencies in Cardiovascular System A. An Approach to Acute Chest Pain," Emergencies in Medicine, vol. 110, Jul. 11, 2024.

19. M. E. Houwing, R. L. Grohssteiner, M. H. Dremmen, F. Atiq, W. M. Bramer, A. P. de Pagter, C. M. Zwaan, T. J. White, M. W. Vernooij, M. H. Cnossen, "Silent cerebral infarcts in patients with sickle cell disease: a systematic review and meta-analysis," BMC Medicine, vol. 18, no. 1, p. 393, Dec. 22, 2020.

20. A. N. Muiru, J. Yang, V. K. Derebail, K. D. Liu, H. I. Feldman, A. Srivastava, Z. Bhat, L. S. Saraf, T. K. Chen, J. He, M. M. Estrella, "Black and white adults with CKD hospitalized with acute kidney injury: findings from the chronic renal insufficiency cohort (CRIC) study," American Journal of Kidney Diseases, vol. 80, no. 5, pp. 610-618, Nov. 1, 2022.

21. G. Sangiorgi, A. Cereda, D. Benedetto, M. Bonanni, G. Chiricolo, L. Cota, E. Martuscelli, F. Greco, "Anatomy, pathophysiology, molecular mechanisms, and clinical management of erectile dysfunction in patients affected by coronary artery disease: a review," Biomedicines, vol. 9, no. 4, p. 432, Apr. 16, 2021.

22. T. Parikh, A. Goti, K. Yashi, N. Ravikumar, N. P. Parmar, N. Dankhara, V. Satodiya, "Pediatric sickle cell disease and stroke: a literature review," Cureus, vol. 15, no. 1, Jan. 20, 2023.

23. K. I. Ataga, L. S. Saraf, and V. K. Derebail, "The nephropathy of sickle cell trait and sickle cell disease," Nature Reviews Nephrology, vol. 18, no. 6, pp. 361-377, Jun. 2022.

24. O. O. Anibire, D. A. Brill, and B. K. Williams Jr, "Sickle cell retinopathy and systemic disease," Annals of Eye Science, vol. 9, p. 11, Jun. 30, 2024.

25. B. Ahmed, M. Arigliani, and A. Gupta, "Respiratory management of acute chest syndrome in children with sickle cell disease," European Respiratory Review, vol. 33, no. 173, Sep. 18, 2024.

26. H. Kaur, F. Aurif, M. Kittaneh, J. P. Chio, and B. H. Malik, "Cardiomyopathy in sickle cell disease," Cureus, vol. 12, no. 8, Aug. 8, 2020.

27. Z. J. Qu, Y. N. Wang, Y. H. Liu, and R. H. Duan, "Association between hematological disorders and gallbladder stones: A review of current evidence," World Journal of Gastrointestinal Surgery, vol. 17, no. 5, p. 105058, May 27, 2025.

28. W. Konarski, T. Poboży, A. Śliwczyński, I. Kotela, J. Krakowiak, M. Hordowicz, and A. Kotela, "Avascular necrosis of femoral head—overview and current state of the art," International Journal of Environmental Research and Public Health, vol. 19, no. 12, p. 7348, Jun. 15, 2022.

29. M. V. Lenti, S. Luu, R. Carsetti, F. Osier, R. Ogwang, O. Nnodu, U. Wiedermann, J. Spencer, F. Locatelli, G. R. Corazza, and A. Di Sabatino, "Asplenia and spleen hypofunction," Nature Reviews Disease Primers, vol. 8, no. 1, p. 71, Nov. 3, 2022.

30. A. Adekile, "The genetic and clinical significance of fetal hemoglobin expression in sickle cell disease," Medical Principles and Practice, vol. 30, no. 3, pp. 201-211, Jun. 30, 2021.

31. E. I. Obeagu and G. U. Obeagu, "Implications of climatic change on sickle cell anemia: A review," Medicine, vol. 103, no. 6, p. e37127, Feb. 2024.

32. E. Jung, J. H. Park, Y. S. Ro, H. H. Ryu, K. C. Cha, S. Do Shin, and S. O. Hwang, "Family history, socioeconomic factors, comorbidities, health behaviors, and the risk of sudden cardiac arrest," Scientific Reports, vol. 13, no. 1, p. 21341, Dec. 2023.

33. A. M. Khayat, B. G. Alshareef, S. F. Alharbi, M. M. AlZahrani, B. A. Alshangity, and N. F. Tashkandi, "Consanguineous marriage and its association with genetic disorders in Saudi Arabia: A review," Cureus, vol. 16, no. 2, p. e53888, Feb. 2024. doi: 10.7759/cureus.53888.

34. H. F. Okab and M. B. Saleh, "Evaluation of the immune status of blood transfusion-dependent thalassemia in Thi-Qar Province/Iraq," Journal of Education for Pure Science-University of Thi-Qar, vol. 9, no. 2, Jun. 2019.

35. A. A. Daak et al., "Sickle cell disease in western Sudan: Genetic epidemiology and predictors of knowledge attitude and practices," Trop. Med. Int. Health, vol. 21, no. 5, pp. 642-653, May 2016. doi: 10.1111/tmi.12689.

36. H. Bakry, R. A. Alaiban, A. A. Alkhyyat, B. H. Alshamrani, R. N. Naitah, and F. Almoayad, "Predictors of consanguinity marriage decision in Saudi Arabia: A pilot study," Healthcare (Basel), vol. 11, no. 13, p. 1925, Jul. 2023. doi: 10.3390/healthcare11131925.

37. S. Patel, D. Chandrakar, P. N. Wasnik, E. Mohapatra, R. Nanda, S. Shah, A. Gupta, "Redefining the reference interval and cut-off values of the hematological and biochemical parameters and deriving a sensitive predictive marker for crisis events in sickle cell disease," Indian J. Clin. Biochem., vol. 40, no. 1, pp. 136-150, Jan. 2025. doi: 10.1007/s12291-023-01158-9.

38. F. Neves, O. A. Menezes Neto, L. B. Polis, S. C. Bassi, D. M. Brunetta, A. C. Silva-Pinto, and I. L. Angulo, "Hematological differences between patients with different subtypes of sickle cell disease on hydroxyurea treatment," Rev. Bras. Hematol. Hemoter., vol. 34, no. 6, pp. 426-429, 2012. doi: 10.5581/1516-8484.20120107.

39. R. D. Silva Brito et al., "Basic biochemical and hematological parameters of structural hemoglobin variants in postpartum women and their respective newborns from Manaus, Amazonas, Brazil," BMC Pregnancy Childbirth, vol. 22, no. 1, p. 936, Dec. 2022. doi: 10.1186/s12884-022-05143-7.

40. C. T. Quinn, E. P. Smith, S. Arbabi, P. K. Khera, C. J. Lindsell, O. Niss, C. H. Joiner, R. S. Franco, and R. M. Cohen, "Biochemical surrogate markers of hemolysis do not correlate with directly measured erythrocyte survival in sickle cell anemia," Am. J. Hematol., vol. 91, no. 12, pp. 1195-1201, Dec. 2016. doi: 10.1002/ajh.24562.

41. N. O. Akinola et al., "Subclinical ischaemic episodes during the steady state of sickle cell anemia," J. Clin. Pathol., vol. 45, no. 10, pp. 902-906, Oct. 1992. doi: 10.1136/jcp.45.10.902.

42. L. Aguiar et al., "Sickle cell anemia - Nitric oxide-related genetic modifiers of hematological and biochemical parameters," Clin. Hemorheol. Microcirc., vol. 64, no. 4, pp. 957-963, 2016. doi: 10.3233/CH-168008.

43. B. Cámara, A. De los Ríos, M. Urizal, M. A. de Buergo, M. J. Varas, R. Fort, and C. Ascaso, "Characterizing the microbial colonization of a dolostone quarry: implications for stone biodeterioration and response to biocide treatments," Microb. Ecol., vol. 62, no. 2, pp. 299-313, Aug. 2011. doi: 10.1007/s00248-011-9815-x.

44. M. O. Quarmyne, F. Bock, S. Lakshmanan, B. K. Attell, A. Snyder, J. Boudreaux, S. Sheth, M. A. Bender, and A. Lal, "Newborn screening for sickle cell disease and thalassemia," JAMA Health Forum, vol. 6, no. 3, pp. e250064-e250064, Mar. 2025.

45. I. K. Kwaifa and I. U. Adekunle, "Current approaches to prenatal diagnosis of sickle cell anaemia," Sokoto J. Med. Lab. Sci., vol. 9, no. 4, pp. 169-180, 2024.

46. E. I. Obeagu, "Potassium dynamics in sickle cell anemia: clinical implications and pathophysiological insights," Ann. Med. Surg., vol. 86, no. 10, pp. 6037-6045, Oct. 2024.

47. R. R. Sales, B. L. Nogueira, J. A. Tosatti, K. B. Gomes, M. R. Luizon, "Do genetic polymorphisms affect fetal hemoglobin (HbF) levels in patients with sickle cell anemia treated with hydroxyurea? A systematic review and pathway analysis," Front. Pharmacol., vol. 12, p. 779497, Jan. 2022.

48. M. Dal Peraro and J. J. Song, "Editorial overview: The future after the cryo-EM resolution revolution," Curr. Opin. Struct. Biol., vol. 58, pp. iii-iv, Oct. 2019. doi: 10.1016/j.sbi.2019.07.007.

49. F. B. Piel, D. C. Rees, M. R. DeBaun, O. Nnodu, B. Ranque, A. A. Thompson, R. E. Ware, M. R. Abboud, A. Abraham, E. E. Ambrose, B. Andemariam, "Defining global strategies to improve outcomes in sickle cell disease: a Lancet Haematology Commission," Lancet Haematol., vol. 10, no. 8, pp. e633-e686, Aug. 2023.

50. E. I. Obeagu and G. U. Obeagu, "Culturally tailored education: a key to adolescent sickle cell disease prevention," Elite J. Public Health, vol. 2, no. 3, pp. 52-62, 2024.

51. J. Menkiszak, A. Chudecka-Głaz, J. Gronwald, R. Bedner, A. Cymbaluk-Płoska, M. Wezowska, D. Zielińska, and I. Rzepka-Górska, "Charakterystyka wybranych aspektów klinicznych u kobiet, nosicielek mutacji genu BRCA1 poddanych operacjom profilaktycznym narzadu płciowego leczonych uprzednio z powodu raka piersi," Ginekol Pol., vol. 84, no. 9, pp. 758-764, Sep. 2013. doi: 10.17772/gp/1636.

52. P. Tibi, R. S. McClure, J. Huang, R. A. Baker, D. Fitzgerald, C. D. Mazer, M. Stone, D. Chu, A. H. Stammers, T. Dickinson, and L. Shore-Lesserson, "STS/SCA/AmSECT/SABM update to the clinical practice guidelines on patient blood management," J. ExtraCorporeal Technol., vol. 53, no. 2, pp. 97-124, Jun. 2021.

53. K. Pinyopornpanish, A. Tantiworawit, A. Leerapun, A. Soontornpun, and S. Thongsawat, "Secondary iron overload and the liver: a comprehensive review," J. Clin. Transl. Hepatol., vol. 11, no. 4, p. 932, Feb. 2023.

54. E. A. Essien, B. F. Winter-Eteng, C. U. Onukogu, D. D. Nkangha, and F. M. Daniel, "Psychosocial challenges of persons with sickle cell anemia: A narrative review," Medicine, vol. 102, no. 47, p. e36147, Nov. 2023.