ORIGINAL ARTICLE
Association between P582S HIF-1A gene polymorphism and hematological parameters among women: A cross-sectional study
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Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, JORDAN
 
 
Online publication date: 2023-05-16
 
 
Publication date: 2023-09-01
 
 
Electron J Gen Med 2023;20(5):em508
 
KEYWORDS
ABSTRACT
Women are prone to low red blood indices due to increased physiological requirements and frequent blood loss in menstrual periods. Hypoxia-inducible factors (HIFs) act as master regulators of oxygen and iron balance. In this study, the association between P582S HIF-1A polymorphism and red blood indices among women was examined. A total of 310 participants were recruited in the study. PCR followed by RFLP technology was used to genotype HIF-1A polymorphism. The mean age of participants was 27.0 years, and the mean BMI was 26.4±7.73 kg/m2. Most of the participants did not exercise (89.1%), and about 21.1% were current tobacco smokers. Frequency of 582S (T) mutant allele was 17.5% while the frequency of 582P (C) wild-type allele was 82.5%. No association was found between P582S HIF-1A and hemoglobin level (p=0.37), red blood cell count (p=0.33), hematocrit (p=0.96), mean body size (p=0.20), mean corpuscular volume (p=0.34), mean corpuscular hemoglobin concentration (p=0.22), red blood cell distribution width (p=0.77), ferritin (p=0.19), and erythropoietin (p=0.15). In addition, no significant differences were found in distribution of P582S genotypes according to age of participants, body mass index, smoking status, and exercise habits (p>0.05). In conclusion, P582S HIF-1A polymorphism may not be associated with red blood indices among women. More studies in other populations are needed to confirm this finding.
 
REFERENCES (53)
1.
Mansour D, Hofmann A, Gemzell-Danielsson K. A review of clinical guidelines on the management of iron deficiency and iron-deficiency anemia in women with heavy menstrual bleeding. Adv Ther. 2021;38(1):201-25. https://doi.org/10.1007/s12325... PMid:33247314 PMCid:PMC7695235.
 
2.
Li J, Gao Q, Tian S, Chen Y, Ma Y, Huang Z. [Menstrual blood loss and iron nutritional status in female undergraduate students]. Wei Sheng Yan Jiu. 2011;40(2):204-5. PMid: 21560310.
 
3.
Perelló J, Rius Tarruella J, Calaf J. Heavy menstrual bleeding and its detection in clinical practice. Med Clin. 2021;157(7):332-8. https://doi.org/10.1016/j.medc... PMid:33840528.
 
4.
Duckitt K. Menorrhagia. BMJ Clin Evid. 2015;2015:0805.
 
5.
Jewson M, Purohit P, Lumsden MA. Progesterone and abnormal uterine bleeding/menstrual disorders. Best Pract Res Clin Obstet Gynaecol. 2020;69:62-73. https://doi.org/10.1016/j.bpob... PMid:32698992.
 
6.
James AH. Heavy menstrual bleeding: work-up and management. Hematology Am Soc Hematol Educ Program. 2016;2016(1):236-42. https://doi.org/10.1182/ashedu... PMid:27913486 PMCid:PMC6142441.
 
7.
Maybin JA, Boswell L, Young VJ, Duncan WC, Critchley HOD. Reduced transforming growth factor-β activity in the endometrium of women with heavy menstrual bleeding. J Clin Endocrinol Metab. 2017;102(4):1299-308. https://doi.org/10.1210/jc.201... PMid:28324043 PMCid:PMC5460733.
 
8.
Albasher G, Bin-Jumah M, Alfarraj S, et al. Prolonged use of finasteride-induced gonadal sex steroids alterations, DNA damage and menstrual bleeding in women. Biosci Rep. 2020;40(2):BSR20191434. https://doi.org/10.1042/bsr201... PMid:31967291 PMCid:PMC7007407.
 
9.
Ke Q, Costa M. Hypoxia-inducible factor-1 (HIF-1). Mol Pharmacol. 2006;70(5):1469-80. https://doi.org/10.1124/mol.10... PMid:16887934.
 
10.
Zhang Q, Han Z, Zhu Y, Chen J, Li W. Role of hypoxia inducible factor-1 in cancer stem cells (review). Mol Med Rep. 2021;23(1):17. https://doi.org/10.3892/mmr.20....
 
11.
Choudhry H, Harris AL. Advances in hypoxia-inducible factor biology. Cell Metab. 2018;27(2):281-98. https://doi.org/10.1016/j.cmet... PMid:29129785.
 
12.
Masoud GN, Li W. HIF-1α pathway: Role, regulation and intervention for cancer therapy. Acta Pharm Sin B. 2015;5(5):378-89. https://doi.org/10.1016/j.apsb... PMid:26579469 PMCid:PMC4629436.
 
13.
Biswas S, Tapryal N, Mukherjee R, Kumar R, Mukhopadhyay CK. Insulin promotes iron uptake in human hepatic cell by regulating transferrin receptor-1 transcription mediated by hypoxia inducible factor-1. Biochim Biophys Acta. 2013;1832(2):293-301. https://doi.org/10.1016/j.bbad... PMid:23160040.
 
14.
Li M, Tang X, Liao Z, et al. Hypoxia and low temperature upregulate transferrin to induce hypercoagulability at high altitude. Blood. 2022;140(19):2063-75. https://doi.org/10.1182/blood.... PMid:36040436.
 
15.
Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood. 2003; 102(3):783-8. https://doi.org/10.1182/blood-... PMid:12663437.
 
16.
Locatelli F, Fishbane S, Block GA, Macdougall IC. Targeting hypoxia-inducible factors for the treatment of anemia in chronic kidney disease patients. Am J Nephrol. 2017;45(3):187-99. https://doi.org/10.1159/000455... PMid:28118622.
 
17.
Hirota K. HIF-α prolyl hydroxylase inhibitors and their implications for biomedicine: A comprehensive review. Biomedicines. 2021;9(5):468. https://doi.org/10.3390/biomed... PMid:33923349 PMCid:PMC8146675.
 
18.
Joharapurkar AA, Pandya VB, Patel VJ, Desai RC, Jain MR. Prolyl hydroxylase inhibitors: A breakthrough in the therapy of anemia associated with chronic diseases. J Med Chem. 2018;61(16):6964-82. https://doi.org/10.1021/acs.jm... PMid:29712435.
 
19.
Das A, Patra M, Dhangadamajhi G. Association of rs11549465 (C1772T) variant of hypoxia-inducible factor-1α with COVID-19 susceptibility. A population-based epidemiological study. Hum Cell. 2021;34(6):1937-40. https://doi.org/10.1007/s13577... PMid:34426956 PMCid:PMC8382105.
 
20.
Torti L, Teofili L, Capodimonti S, et al. Hypoxia-inducible factor-1α(Pro-582-Ser) polymorphism prevents iron deprivation in healthy blood donors. Blood Transfus. 2013;11(4):553-7. https://doi.org/10.2450/2013.0....
 
21.
Döring F, Onur S, Fischer A, et al. A common haplotype and the Pro582Ser polymorphism of the hypoxia-inducible factor-1alpha (HIF1A) gene in elite endurance athletes. J Appl Physiol (1985). 2010;108(6):1497-500. https://doi.org/10.1152/japplp... PMid:20299614.
 
22.
Ahmetov, II, Hakimullina AM, Lyubaeva EV, Vinogradova OL, Rogozkin VA. Effect of HIF1A gene polymorphism on human muscle performance. Bull Exp Biol Med. 2008;146(3):351-3. https://doi.org/10.1007/s10517... PMid:19240858.
 
23.
Blanco-Rojo R, Toxqui L, López-Parra AM, et al. Influence of diet, menstruation and genetic factors on iron status: a cross-sectional study in Spanish women of childbearing age. Int J Mol Sci. 2014;15(3):4077-87. https://doi.org/10.3390/ijms15... PMid:24663082 PMCid:PMC3975385.
 
24.
Gerger A, El-Khoueiry A, Zhang W, et al. Pharmacogenetic angiogenesis profiling for first-line bevacizumab plus oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Clin Cancer Res. 2011;17(17): 5783-92. https://doi.org/10.1158/1078-0... PMid:21791631 PMCid:PMC3174848.
 
25.
Khabour OF, Bani-Ahmad MA, Hammash NM. Association between polymorphisms in erythropoietin gene and upper limit haematocrit levels among regular blood donors. Transfus Clin Biol. 2012;19(6):353-7. https://doi.org/10.1016/j.trac... PMid:23142128.
 
26.
Rolfs A, Kvietikova I, Gassmann M, Wenger RH. Oxygen-regulated transferrin expression is mediated by hypoxia-inducible factor-1. J Biol Chem. 1997;272(32):20055-62. https://doi.org/10.1074/jbc.27... PMid:9242677.
 
27.
Prior SJ, Hagberg JM, Phares DA, et al. Sequence variation in hypoxia-inducible factor 1alpha (HIF1A): Association with maximal oxygen consumption. Physiol Genomics. 2003;15(1):20-6. https://doi.org/10.1152/physio... PMid:12865501.
 
28.
McPhee JS, Perez-Schindler J, Degens H, et al. HIF1A P582S gene association with endurance training responses in young women. Eur J Appl Physiol. 2011;111(9):2339-47. https://doi.org/10.1007/s00421... PMid:21344271.
 
29.
Liu HP, Hu Y. [Association between polymorphisms of HIF-1alpha, eNOS genes and individual variation in response to hypoxia training]. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2006;22(4):434-8. PMid:21155268.
 
30.
Lessi F, Mazzanti CM, Tomei S, et al. VHL and HIF-1α: Gene variations and prognosis in early-stage clear cell renal cell carcinoma. Med Oncol. 2014;31(3):840. https://doi.org/10.1007/s12032... PMid:24446253.
 
31.
Meka PB, Cingeetham A, Nanchari SR, et al. HIF-1α (1772C>T) polymorphism as marker for breast cancer development. Tumour Biol. 2015;36(5):3215-20. https://doi.org/10.1007/s13277... PMid:25510668.
 
32.
Fu XS, Choi E, Bubley GJ, Balk SP. Identification of hypoxia-inducible factor-1alpha (HIF-1alpha) polymorphism as a mutation in prostate cancer that prevents normoxia-induced degradation. Prostate. 2005;63(3):215-21. https://doi.org/10.1002/pros.2... PMid:15538748.
 
33.
Xu J, Xu L, Li L, You Q, Cha L. HIF-1α C1772T polymorphism and gastrointestinal tract cancer risk: A meta-analysis and meta-regression analysis. Genet Test Mol Biomarkers. 2013;17(12):918-25. https://doi.org/10.1089/gtmb.2... PMid:24063654.
 
34.
Resar JR, Roguin A, Voner J, et al. Hypoxia-inducible factor 1alpha polymorphism and coronary collaterals in patients with ischemic heart disease. Chest. 2005;128(2):787-91. https://doi.org/10.1378/chest.... PMid:16100168.
 
35.
Ekberg NR, Eliasson S, Li YW, et al. Protective effect of the HIF-1A Pro582Ser polymorphism on severe diabetic retinopathy. J Diabetes Res. 2019;2019:2936962. https://doi.org/10.1155/2019/2... PMid:31214621 PMCid:PMC6535890.
 
36.
Pichu S, Sathiyamoorthy J, Krishnamoorthy E, Umapathy D, Viswanathan V. Impact of the hypoxia inducible factor-1α (HIF-1α) pro582ser polymorphism and its gene expression on diabetic foot ulcers. Diabetes Res Clin Pract. 2015;109(3):533-40. https://doi.org/10.1016/j.diab... PMid:26113285.
 
37.
Zhao J, Zhang L-X, Wang Y-T, Li Y, Chen Md H-L. Genetic polymorphisms and the risk of diabetic foot: A systematic review and meta-analyses. Int J Low Extrem Wounds. 2022;21(4):574-87. https://doi.org/10.1177/153473... PMid:33327826.
 
38.
Harati-Sadegh M, Kohan L, Teimoori B, Mehrabani M, Salimi S. The association of the placental Hypoxia-inducible factor1-α polymorphisms and HIF1-α mRNA expression with preeclampsia. Placenta. 2018;67:31-7. https://doi.org/10.1016/j.plac... PMid:29941171.
 
39.
Hlatky MA, Quertermous T, Boothroyd DB, et al. Polymorphisms in hypoxia inducible factor 1 and the initial clinical presentation of coronary disease. Am Heart J. 2007; 154(6):1035-42. https://doi.org/10.1016/j.ahj.... PMid:18035072.
 
40.
Paek J, Oh Y, Kim J, Lee JH. Single nucleotide polymorphisms in HIF-1α gene and residual ridge resorption (RRR) of mandible in Korean population. Gene Exp. 2015;16(3):137-44. https://doi.org/10.3727/105221... PMid:25700369 PMCid:PMC8750342.
 
41.
Urganci BE, Acikbas I, Er FR. Investigation of immunovascular polymorphisms and intersections in psoriasis. Indian J Dermatol. 2019;64(3):187-91. https://doi.org/10.4103/ijd.IJ... PMid:31148856 PMCid:PMC6537683.
 
42.
Wang X, Liu Y, Ren H, et al. Polymorphisms in the hypoxia-inducible factor-1α gene confer susceptibility to pancreatic cancer. Cancer Biol Ther. 2011;12(5):383-7. https://doi.org/10.4161/cbt.12... PMid:21709439.
 
43.
Gabbasov RT, Arkhipova AA, Borisova AV, et al. The HIF1A gene Pro582Ser polymorphism in Russian strength athletes. J Strength Cond Res. 2013;27(8):2055-8. https://doi.org/10.1519/JSC.0b... PMid:23222085.
 
44.
Hernández-Molina G, Rodríguez-Pérez JM, Fernandez-Torres, J, et al. HIF1A (rs11549465) and AKNA (rs10817595) gene polymorphisms are associated with primary Sjögren’s syndrome. Biomed Res Int. 2017;2017:5845849. https://doi.org/10.1155/2017/5... PMid:28484714 PMCid:PMC5397622.
 
45.
Strauss E, Waliszewski K, Oszkinis G, Staniszewski R. [Gene-environment interaction for the HIF1-A 1772C>T polymorphisms and cigarette smoking increase susceptibility to abdominal aortic aneurysm]. Przegl Lek. 2012;69(10):744-9. PMid:23421024.
 
46.
Tanimoto K, Yoshiga K, Eguchi H, et al. Hypoxia-inducible factor-1alpha polymorphisms associated with enhanced transactivation capacity, implying clinical significance. Carcinogenesis. 2003;24(11):1779-83. https://doi.org/10.1093/carcin... PMid:12919954.
 
47.
Bosnyák E, Trájer E, Alszászi G, et al. Lack of association between the GNB3 rs5443, HIF1A rs11549465 polymorphisms, physiological and functional characteristics. Ann Hum Genet. 2020;84(5):393-9. https://doi.org/10.1111/ahg.12... PMid:32391916.
 
48.
Wang L, Tang Y, Chen Y. HIF1A gene rs10873142 polymorphism is associated with risk of chronic obstructive pulmonary disease in a Chinese Han population: A case-control study. Biosci Rep. 2018;38(2):BSR20171309. https://doi.org/10.1042/bsr201... PMid:29339421 PMCid:PMC5843754.
 
49.
López-Reyes A, Rodríguez-Pérez JM, Fernández-Torres J, et al. The HIF1A rs2057482 polymorphism is associated with risk of developing premature coronary artery disease and with some metabolic and cardiovascular risk factors. The genetics of atherosclerotic disease (GEA) Mexican study. Exp Mol Pathol. 2014;96(3):405-10. https://doi.org/10.1016/j.yexm... PMid:24769354.
 
50.
Alonso Pérez JL, Martín Pérez S, Battaglino A, Villafañe JH, Alonso-Sal A, Sánchez Romero EA. An up-date of the muscle strengthening exercise effectiveness in postmenopausal women with osteoporosis: A qualitative systematic review. J Clin Med. 2021;10(11):2229. https://doi.org/10.3390/jcm101... PMid:34063906 PMCid:PMC8196674.
 
51.
Stegen S, Deprez S, Eelen G, et al. Adequate hypoxia inducible factor 1α signaling is indispensable for bone regeneration. Bone. 2016;87:176-86. https://doi.org/10.1016/j.bone... PMid:27058876.
 
52.
Bennett D, O’Shea D, Ferguson J, Morris D, Seoighe C. Controlling for background genetic effects using polygenic scores improves the power of genome-wide association studies. Sci Rep. 2021;11(1):19571. https://doi.org/10.1038/s41598... PMid:34599249 PMCid:PMC8486788.
 
53.
Strauss E, Waliszewski K, Oszkinis G, Staniszewski R. Polymorphisms of genes involved in the hypoxia signaling pathway and the development of abdominal aortic aneurysms or large-artery atherosclerosis. J Vasc Surg. 2015;61(5):1105-13.e3. https://doi.org/10.1016/j.jvs.... PMid:24657063.
 
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