Transferrin receptor levels and polymorphism of its gene in age-related macular degeneration
Languages of publication
The aim of the present study was to investigate the association of age related macular degeneration (AMD) risk with some aspects of iron homeostasis: iron concentration in serum, level of soluble transferrin receptor (sTfR), and transferrin receptor (TFRC) genetic variability. Four hundred and ninety one AMD patients and 171 controls were enrolled in the study. Restriction fragment length polymorphism PCR was employed to genotype polymorphisms of the TFRC gene, and colorimetric assays were used to determine the level of iron and sTfR. Multiple logistic regression was applied for all genotype/allele-related analyses and the ANOVA test for iron and sTfR serum level comparison. We found that the genotypes and alleles of the c.-253G > A polymorphism of the TFRC gene were associated with AMD risk and this association was modulated by smoking status, AMD family history, living environment (rural/urban), body mass index and age. The levels of sTfR was higher in AMD patients than controls, whereas concentrations of iron did not differ in these two groups. No association was found between AMD occurrence and the p.Gly142Ser polymorphism of the TRFC gene. The results obtained suggest that transferrin receptor and variability of its gene may influence AMD risk.
- Age-Related Eye Disease Study Research Group (2000) Risk factors associated with age-related macular degeneration. A case-control study in the age-related eye disease study: age-related eye disease study report number 3. Ophthalmology 107: 2224-2232.
- Ambati J, Ambati BK, Yoo SH, Ianchulev S, Adamis AP (2003) Age-related macular degeneration. Surv Ophthalmol 48: 257-293.
- Bao W, Rong Y, Rong S, Liu L (2012) Dietary iron intake, body iron stores, and the risk of type 2 diabetes: a systematic review and meta-analysis. BMC Med 10:
- Blasiak J, Szaflik J, Szaflik JP (2011) Implications of altered iron homeostasis for age-related macular degeneration. Front Biosci 16: 1551-1559.
- Brissot P, Ropert M, Le Lan C, Loréal O (2012) Non-transferrin bound iron: A key role in iron overload and iron toxicity. Biochim Biophys Acta 1820: 403-410.
- Buch H, Vinding T, la Cour M, Jensen GB, Prause JU, Nielsen NV (2005) Risk factors for age-related maculopathy in 14-year follow-up study: the Copenhagen City Eye Study. Acta Ophtalmol Scand 83: 409-418.
- Chen H, Lukas TJ, Du N, Suyeoka G, Neufeld AH (2009) Dysfunction of the retinal pigment epithelium with age: increased iron decreases phagocytosis and lysosomal activity. Invest Ophthalmol Vis Sci 50: 1895-1902.
- Chiu CJ, Conley YP, Gorin MB, Gensler G, Lai CQ, Shang F, Taylor A (2001) Associations between genetic polymorphisms of insulin-like growth factor axis genes and risk for age-related macular degeneration. Invest Ophthalmol Vis Sci 52: 9099-9107.
- Clemons TE, Milton RC, Klein R, Seddon JM, Ferris FL 3rd (2005) Risk factors for the incidence of advanced age-related macular degeneration in the Age-Related Disease Study (AREDS): AREDS report No. 19. Ophthalmology 112: 533-539.
- Coleman HR, Chan CC, Ferris FL 3rd, Chew EY (2008) Age-related macular degeneration. Lancet 372: 1835-1845.
- Cong R, Zhou B, Sun Q, Gu H, Tang N, Wang B (2008) Smoking and the risk of age-related macular degeneration: a meta-analysis. Ann Epidemiol 18: 647-656.
- Dayem Ullah AZ, Lemoine NR, Chelala C (2012) SNPnexus: a web server for functional annotation of novel and publicly known genetic variants. Nucleic Acids Res 40 (Web Server issue): W65-W70.
- Ding X, Patel M, Chan CC (2009) Molecular pathology of age-related macular degeneration. Prog Retin Eye Res 28: 1-18.
- Eaton JW, Qian M (2002) Molecular bases of cellular iron toxicity. Free Radic Biol Med 32: 833-840.
- Edison ES, Bajel A, Chandy M (2008) Iron homeostasis: new players, newer insights. Eur J Haematol 81: 411-424.
- Feret A, Steinweg S, Griffi HC, Glover S (2007) Macular degeneration: types, causes, and possible interventions. Geriatr Nurs 28: 387-392.
- Fernández-Real JM, Mercader JM, Ortega FJ, Moreno-Navarrete JM, López-Romero P, Ricart W (2010) Transferrin receptor-1 gene polymorphisms are associated with type 2 diabetes. Eur J Clin Invest 40: 600-607.
- Finger RP, Fimmers R, Holz FG, Scholl HP (2011) Prevalence and causes of registered blindness in the largest federal state of Germany. Br J Ophthalmol 95: 1061-1067.
- Frank RN, Puklin JE, Stock C, Canter LA (2000) Race, iris color, and age-related macular degeneration. Trans Am Ophtalmol Soc 98: 109-117.
- Ganesh SK (2009) Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium. Nat Genet 41: 1191-1198.
- Hammond CJ, Webster AR, Snieder H, Bird AC, Gilbert CE, Spector TD (2002) Genetic influence on early age-related maculopathy: a twin study. Ophthalmology 109: 730-736.
- He X, Hahn P, Iacovelli J, Wong R, King C, Bhisitkul R, Massaro-Giordano M, Dunaief JL (2007) Iron homeostasis and toxicity in retinal degeneration. Prog Retin Eye Res 26: 649-673.
- Hentze MW, Muckenthaler MU, Andrews NC (2004) Balancing acts: molecular control of mammalian iron metabolism. Cell 117: 285-297.
- Hogg RE, Chakravarthy U (2006) Visual function and dysfunction in early and late age-related maculopathy. Prog Retin Eye Res 25: 249-276.
- Jacobs A (1976) An intracellular transit iron pool. Ciba Found Symp (51): 91-106.
- Jia S, Liang M, Guo LH (2008) Photoelectrochemical detection of oxidative DNA damage induced by Fenton reaction with low concentration and DNA-associated Fe2+. J Phys Chem B 112: 4461-4464.
- Jomova K, Valko M (2011) Advances in metal-induced oxidative stress and human disease. Toxicology 283: 65-87.
- Kaarniranta K, Salminen A, Haapasalo H, Soininen H, Hiltunen M (2011) Age-related macular degeneration (AMD): Alzheimer's disease in the eye? J Alzheimers Dis 24: 615-631.
- Kakhlon O, Cabantchik ZI (2002) The labile iron pool: characterization, measurement, and participation in cellular processes. Free Radic Biol Med 33: 1037-1046.
- Klein BE, Klein R, Lee KE (1998) Incidence of age-related cataract: the Beaver Dam Eye Study. Arch Ophthalmol 116: 219-225.
- Klein ML, Mauldin WM, Stoumbos VD (1994) Heredity and age-related macular degeneration. Observations in monozygotic twins. Arch Ophthalmol 112: 932-937.
- Klein R, Klein BE, Tomany SC, Cruickshanks KJ (2003) The association of cardiovascular disease with the long-term incidence of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology 110: 636-643.
- Kohgo Y, Ikuta K, Ohtake T, Torimoto Y, Kato J (2008) Body iron metabolism and pathophysiology of iron overload. Int J Hematol 88: 7-154.
- McConnell V, Silvestri G (2005) Age-related macular degeneration. Ulster Med J 74: 82-92.
- Montezuma SR, Sobrin L, Seddon JM (2007) Review of genetics in age-related macular degeneration. Semin Ophthalmol 22: 229-240.
- Muñoz M, Villar I, García-Erce JA (2009) An update on iron physiology. World J Gastroenterol 15: 4617-4626.
- Nadadur SS, Srirama K, Mudipalli A (2008) Iron transport & homeostasis mechanisms: their role in health & disease. Indian J Med Res 128: 533-544.
- Njajou OT, Alizadeh BZ, Aulchenko Y, Zillikens MC, Pols HA, Oosstra BA, Swinkels DW, van Duijn CM (2006) Heritability of serum iron, ferritin and transferrin saturation in a genetically isolated population, the Erasmus Rucphen Family (ERF) Study. Duijn Hum Hered 61: 222-228.
- Owen CG, Jarrar Z, Wormald R, Cook DG, Fletcher AE, Rudnicka AR (2012) The estimated prevalence and incidence of late stage age related macular degeneration in the UK. Br J Ophthalmol 96: 752-756.
- Ponka P, Lok CN (1999) The transferrin receptor: role in health and disease. Int J Biochem Cell Biol 31: 1111-1137.
- Sanfilippo PG, Hewitt AW, Hammond CJ, Mackey DA (2010) The heritability of ocular traits. Surv Ophthalmol 55: 561-583.
- SanGiovanni JP, Chew EY, Clemons TE, Davis MD, Ferris FL 3rd, Gensler GR, Kurinij N, Lindblad AS, Milton RC, Seddon JM, Sperduto RD; Age-Related Eye Disease Study Research Group. (2007) The relationship of dietary lipid intake and age-related macular degeneration in a case-control study. AREDS Report No. 20. Arch Ophthalmol 125: 671-679.
- Scholl HP, Fleckenstein M, Charbel Issa P, Keilhauer C, Holz FG, Weber BH (2007) An update on the genetics of age-related macular degeneration. Mol Vis 13: 196-205.
- Seddon JM, George S, Rosner B (2006a) Cigarette smoking, fish consumption, omega-3 fatty acid intake, and associations with age-related macular degeneration: the US Twin Study of Age-Related Macular Degeneration. Arch Ophthalmol 124: 995-1001.
- Seddon JM, George S, Rosner B, Klein ML (2006b) CFH gene variant, Y402H, and smoking, body mass index, environmental associations with advanced age-related macular degeneration. Hum Hered 61: 157-165.
- Shahid H, Khan JC, Cipriani V, Sepp T, Matharu BK, Bunce C, Harding SP, Clayton DG, Moore AT, Yates JR (2012) Genetic Factors in AMD Study Group. Age-related macular degeneration: the importance of family history as a risk factor. Br J Ophthalmol 96: 427-431.
- Tan JS, Mitchell P, Kifley A, Flood V, Smith W, Wang JJ (2007) Smoking and the long-term incidence of age-related macular degeneration - the blue mountains eye study. Arch Ophthalmol 125: 1089-1095.
- Theil EC, Goss DJ (2009) Living with iron (and oxygen): questions and answers about iron homeostasis. Chem Rev 109: 4568-4579.
- Tomany SC, Wang JJ, Van Leeuwen R, Klein R, Mitchell P, Vingerling JR, Klein BE, Smith W, De Jong PT (2004) Risk factors for incident age-related macular degeneration: pooled findings from 3 continents. Ophthalmology 111: 1280-1287.
- Vojnikovic B, Njiric S, Coklo M, Spanjol J (2007) Ultraviolet sun radiation and incidence of age-related macular degeneration on Croatian Island Rab. Coll Antropol 31 Suppl 1: 43-44.
- Wang JJ, Ross RJ, Tuo J, Burlutsky G, Tan AG, Chan CC, Favaloro EJ, Williams A, Mitchell P (2008) The LOC387715 polymorphism, inflammatory markers, smoking, and age-related macular degeneration. A population-based case-control study. Ophthalmology 115: 693-699.
- Wong RW, Richa DC, Hahn P, Green WR, Dunaief JL (2007) Iron toxicity as a potential factor in AMD. Retina 27: 997-1003.
- Wysokinski D, Danisz K, Blasiak J, Dorecka M, Romaniuk D, Szaflik J, Szaflik JP (2013) An association of transferrin gene polymorphism and serum transferrin levels with age-related macular degeneration. Exp Eye Res 106: 14-23.
- Wysokinski D, Szaflik J, Sklodowska A, Kolodziejska U, Dorecka M, Romaniuk D, Wozniak K, Blasiak J, Szaflik JP (2011) The A Allele of the -576G > A polymorphism of the transferrin gene is associated with the increased risk of age-related macular degeneration in smokers. Tohoku J Exp Med 223: 253-61.
- Yuan HY, Chiou JJ, Tseng WH, Liu CH, Liu CK, Lin YJ, Wang HH, Yao A, Chen YT, Hsu CN (2006) FASTSNP: an always up-to-date and extendable service for SNP function analysis and prioritization. Nucleic Acids Res 34 (Web Server issue): W635-641.
Publication order reference