Associations of TF Gene Polymorphisms with the Risk of Ischemic Stroke

Overview

Journal J Mol Neurosci

Specialties Molecular Biology
Neurology

Date 2018 Jun 25

PMID 29936663

Authors

Yi Cai

Shaofang Wu

Chaosheng Zeng

Qingjie Su

Jingxia Zhou

Pengxiang Li

Mingming Dai

Desheng Wang

Faqing Long

Affiliations

Soon will be listed here.

Abstract

Ischemic stroke (IS) is the main cause of mortality and disability in China; thus, this study aimed to examine the association between six variants and their haplotypes within the transferrin (TF) gene and the risk of IS in the Southern Chinese Han population. Genotyping was performed using the Sequenom MassARRAY platform for 249 IS patients and 249 age- and sex-matched controls. The association between polymorphisms and IS risk was tested by Chi squared test and haplotype and stratification analysis. Odds ratios (ORs) and confidence intervals (CIs) were estimated by unconditional logistic regression analysis. The results of genetic model analyses indicated that the two SNPs (rs1880669 and rs2692695) were associated with decreased IS risk under the co-dominant, dominant, and additive models. Additionally, rs4525863 was also associated with decreased IS risk both under the dominant and additive models in males. Moreover, the CG haplotype of TF (rs1880669 and rs2692695) was significantly associated with a decreased risk of IS in the total population and males. Our findings suggested that polymorphisms (rs4525863, rs1880669, and rs2692695) of the TF gene might be a protective factor for IS in Southern Chinese Han population. Further large prospective studies are required to confirm these findings.

References

Carbonell T, Rama R . Iron, oxidative stress and early neurological deterioration in ischemic stroke. Curr Med Chem. 2007; 14(8):857-74. DOI: 10.2174/092986707780363014. View

Constantine C, Anderson G, Vulpe C, McLaren C, Bahlo M, Yeap H . A novel association between a SNP in CYBRD1 and serum ferritin levels in a cohort study of HFE hereditary haemochromatosis. Br J Haematol. 2009; 147(1):140-9. PMC: 2767327. DOI: 10.1111/j.1365-2141.2009.07843.x. View

Anic G, Madden M, Thompson R, Nabors L, Olson J, LaRocca R . Toenail iron, genetic determinants of iron status, and the risk of glioma. Cancer Causes Control. 2013; 24(12):2051-8. PMC: 3823695. DOI: 10.1007/s10552-013-0281-2. View

Wojcik K, Synowiec E, Jimenez-Garcia M, Kaminska A, Polakowski P, Blasiak J . Polymorphism of the transferrin gene in eye diseases: keratoconus and Fuchs endothelial corneal dystrophy. Biomed Res Int. 2013; 2013:247438. PMC: 3857736. DOI: 10.1155/2013/247438. View

Liu L, Wang D, Wong K, Wang Y . Stroke and stroke care in China: huge burden, significant workload, and a national priority. Stroke. 2011; 42(12):3651-4. DOI: 10.1161/STROKEAHA.111.635755. View

Gillum R, Sempos C, Makuc D, Looker A, Chien C, Ingram D . Serum transferrin saturation, stroke incidence, and mortality in women and men. The NHANES I Epidemiologic Followup Study. National Health and Nutrition Examination Survey. Am J Epidemiol. 1996; 144(1):59-68. DOI: 10.1093/oxfordjournals.aje.a008855. View

Benyamin B, McRae A, Zhu G, Gordon S, Henders A, Palotie A . Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levels. Am J Hum Genet. 2008; 84(1):60-5. PMC: 2668053. DOI: 10.1016/j.ajhg.2008.11.011. View

Allen C, Bayraktutan U . Oxidative stress and its role in the pathogenesis of ischaemic stroke. Int J Stroke. 2009; 4(6):461-70. DOI: 10.1111/j.1747-4949.2009.00387.x. View

Gkouvatsos K, Papanikolaou G, Pantopoulos K . Regulation of iron transport and the role of transferrin. Biochim Biophys Acta. 2011; 1820(3):188-202. DOI: 10.1016/j.bbagen.2011.10.013. View

10.

Turtzo L, McCullough L . Sex-specific responses to stroke. Future Neurol. 2010; 5(1):47-59. PMC: 2827821. DOI: 10.2217/fnl.09.66. View

11.

Gomme P, McCann K, Bertolini J . Transferrin: structure, function and potential therapeutic actions. Drug Discov Today. 2005; 10(4):267-73. DOI: 10.1016/S1359-6446(04)03333-1. View

12.

Qu M, Yue W, Tang F, Wang L, Han Y, Zhang D . Polymorphisms of Transferrin gene are associated with schizophrenia in Chinese Han population. J Psychiatr Res. 2007; 42(11):877-83. DOI: 10.1016/j.jpsychires.2007.10.005. View

13.

Feigin V, Lawes C, Bennett D, Barker-Collo S, Parag V . Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol. 2009; 8(4):355-69. DOI: 10.1016/S1474-4422(09)70025-0. View

14.

van der A D, Grobbee D, Roest M, Marx J, Voorbij H, van der Schouw Y . Serum ferritin is a risk factor for stroke in postmenopausal women. Stroke. 2005; 36(8):1637-41. DOI: 10.1161/01.STR.0000173172.82880.72. View

15.

McLaren C, McLachlan S, Garner C, Vulpe C, Gordeuk V, Eckfeldt J . Associations between single nucleotide polymorphisms in iron-related genes and iron status in multiethnic populations. PLoS One. 2012; 7(6):e38339. PMC: 3382217. DOI: 10.1371/journal.pone.0038339. View

16.

Erdemoglu A, Ozbakir S . Serum ferritin levels and early prognosis of stroke. Eur J Neurol. 2002; 9(6):633-7. DOI: 10.1046/j.1468-1331.2002.00472.x. View

17.

Zhang P, Yang Z, Zhang C, Lu Z, Shi X, Zheng W . Association study between late-onset Alzheimer's disease and the transferrin gene polymorphisms in Chinese. Neurosci Lett. 2003; 349(3):209-11. DOI: 10.1016/s0304-3940(03)00837-1. View

18.

Lieu P, HEISKALA M, Peterson P, Yang Y . The roles of iron in health and disease. Mol Aspects Med. 2001; 22(1-2):1-87. DOI: 10.1016/s0098-2997(00)00006-6. View

19.

Bejot Y, Daubail B, Giroud M . Epidemiology of stroke and transient ischemic attacks: Current knowledge and perspectives. Rev Neurol (Paris). 2016; 172(1):59-68. DOI: 10.1016/j.neurol.2015.07.013. View

20.

Ong S, Ho J, Ho B, Ding J . Iron-withholding strategy in innate immunity. Immunobiology. 2006; 211(4):295-314. DOI: 10.1016/j.imbio.2006.02.004. View