Human Leukocyte Antigens (HLA) Genes Association in Type 1 Diabetic Nephropathy

Author(s): Esma Mihoubi, Habiba Amroun, Rachida Raache*, Faiza Bouldjennet, Fethi Meçabih, Malha Azzouz, Aissa Boudiba, Souad Mahgoun, Malika Akachouche, Nawel Salhi, Chafia Touil-Boukoffa, Mohamed C. Abbadi, Nabila Attal.

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
(Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders)

Volume 19 , Issue 8 , 2019

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Abstract:

Background: Diabetic nephropathy is a common worldwide multifactorial disease where involvement of genetic factors is well etablished. The aim of this study was to investigate the HLA genes implication in the development of type 1 diabetic nephropathy.

Methods: We performed a case- control study where one hundred and fifty subjects were examined. Patients were divided in two groups; with and without type 1 diabetic nephropathy. HLA typing was performed using Polymerase Chain Reaction- Sequence Specific Oligonucleotide (PCR- SSO) method. HLA association to clinical phenotype and HLA haplotype analysis was also investigated.

Results: HLA B*51 is increased in patients without type 1 diabetic nephropathy (7.14% vs. 0 %, P <0.05, OR= 0), however no other studied alleles seem to have any effect (all P>0.05). Haplotype analysis also does not reveal any significant association, however, A*02-B*18-DRB1*03-DQA1*05- DQB1*03 haplotype shows a tendency to be associated with the development of diabetic nephropathy (P = 0.05).

Conclusion: These results suggest a protective effect of HLA B*51 allele from type 1 diabetic nephropathy. However, further studies are required in order to clarify its potential implication as a protective marker.

Keywords: Type 1diabetes, diabetic nephropathy, class I HLA genes, class II HLA genes, alleles, analysis, haplotype analysis.

[1]
Collins, A.J.; Foley, R.N.; Chavers, B.; Gilbertson, D.; Herzog, C.; Johansen, K.; Kasiske, B.; Kutner, N.; Liu, J.; St Peter, W.; Guo, H.; Gustafson, S.; Heubner, B.; Lamb, K.; Li, S.; Li, S.; Peng, Y.; Qiu, Y.; Roberts, T.; Skeans, M.; Snyder, J.; Solid, C.; Thompson, B.; Wang, C.; Weinhand, E.; Zaun, D.; Arko, C.; Chen, S.C.; Daniels, F.; Ebben, J.; Frazier, E.; Hanzlik, C.; Johnson, R.; Sheets, D.; Wang, X.; Forrest, B.; Constantini, E.; Everson, S.; Eggers, P.; Agodoa, L. United states renal data system 2011 annual data report: Atlas of chronic kidney disease & end-stage renal disease in the united states. Am. J. Kidney Dis., 2012, 59(1)(Suppl. 1), e1-e420.
[2]
Sowers, J.R.; Epstein, M. Diabetes mellitus and associated hypertension, vascular disease, and nephropathy. An update. Hypertension, 1995, 26(6 Pt 1), 869-879.
[http://dx.doi.org/10.1161/01.HYP.26.6.869] [PMID: 7490142]
[3]
de Ferranti, S.D.; de Boer, I.H.; Fonseca, V.; Fox, C.S.; Golden, S.H.; Lavie, C.J.; Magge, S.N.; Marx, N.; McGuire, D.K.; Orchard, T.J.; Zinman, B.; Eckel, R.H. Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. Diabetes Care, 2014, 37(10), 2843-2863.
[http://dx.doi.org/10.2337/dc14-1720] [PMID: 25114297]
[4]
Velez, MG The Role of the Immune System in the Pathogenesis of Dia-betic Nephropathy. J. Nephrology and Ther., 2012. S 2:007
[5]
Merta, M.; Reiterova, J.; Rysava, R.; Kmentova, D.; Tesar, V. Genetics of diabetic nephropathy. Nephrol Dial Transplan,, 2003, 24(18)
[6]
Doria, A.; Warram, J.H.; Krolewski, A.S. Genetic susceptibility to nephropathy in insulin-dependent diabetes: from epidemiology to molecular genetics. Diabetes Metab. Rev., 1995, 11(4), 287-314.
[http://dx.doi.org/10.1002/dmr.5610110402] [PMID: 8718493]
[7]
Ahlqvist, E.; van Zuydam, N.R.; Groop, L.C.; McCarthy, M.I. The genetics of diabetic complications. Nat. Rev. Nephrol., 2015, 11(5), 277-287.
[http://dx.doi.org/10.1038/nrneph.2015.37] [PMID: 25825086]
[8]
Thorsby, E.; Lie, B.A. HLA associated genetic predisposition to autoimmune diseases: Genes involved and possible mechanisms. Transpl. Immunol., 2005, 14(3-4), 175-182.
[http://dx.doi.org/10.1016/j.trim.2005.03.021] [PMID: 15982560]
[9]
Robson, K.J.; Ooi, J.D.; Holdsworth, S.R.; Rossjohn, J.; Kitching, A.R. HLA and kidney disease: from associations to mechanisms. Nat. Rev. Nephrol., 2018, 14(10), 636-655.
[http://dx.doi.org/10.1038/s41581-018-0057-8] [PMID: 30206339]
[10]
Bakay, M.; Pandey, R.; Hakonarson, H. Genes involved in type 1 diabetes: an update. Genes (Basel), 2013, 4(3), 499-521.
[http://dx.doi.org/10.3390/genes4030499] [PMID: 24705215]
[11]
Noble, J.A.; Valdes, A.M.; Varney, M.D.; Carlson, J.A.; Moonsamy, P.; Fear, A.L.; Lane, J.A.; Lavant, E.; Rappner, R.; Louey, A.; Concannon, P.; Mychaleckyj, J.C.; Erlich, H.A. HLA class I and genetic susceptibility to type 1 diabetes: results from the Type 1 Diabetes Genetics Consortium. Diabetes, 2010, 59(11), 2972-2979.
[http://dx.doi.org/10.2337/db10-0699] [PMID: 20798335]
[12]
Raache, R.; Benyahia, A.; Amroun, H.; Nabila, A.; Hamiane, W.; Azzouz, M. Comparison of HLA class II. antigens between three type 1 diabetes groups in the central region of Algeria. The SA jour-nal of diabetes and vascular disease, 2010, 7(4), 149-153.
[13]
Barbosa, J. Is diabetic microangiopathy genetically heterogeneous? HLA and diabetic nephropathy. Horm. Metab. Res. Suppl., 1981, 11, 77-80.
[PMID: 6947952]
[14]
Lipner, E.M.; Tomer, Y.; Noble, J.A.; Monti, M.C.; Lonsdale, J.T.; Corso, B.; Stewart, W.C.; Greenberg, D.A. HLA class I and II alleles are associated with microvascular complications of type 1 diabetes. Hum. Immunol., 2013, 74(5), 538-544.
[http://dx.doi.org/10.1016/j.humimm.2013.01.013] [PMID: 23376458]
[15]
Razanskaite-Virbickiene, D.; Danyte, E.; Zalinkevicius, R. DRB1*03 as a risk factor for microalbuminuria in same dura-tion of type 1 diabetes: a case control study. BMC Nephro.,, 2016, 17(38), 016-0252.
[16]
Cruickshanks, K.J.; Vadheim, C.M.; Moss, S.E.; Roth, M.P.; Riley, W.J.; Maclaren, N.K.; Langfield, D.; Sparkes, R.S.; Klein, R.; Rotter, J.I. Genetic marker associations with proliferative retinopathy in persons diagnosed with diabetes before 30 yr of age. Diabetes, 1992, 41(7), 879-885.
[http://dx.doi.org/10.2337/diab.41.7.879] [PMID: 1612203]
[17]
Harindhanavudhi, T.; Mauer, M. Autoimmunity and Inflammation in Diabetic Nephropathy.Encyclopedia of Medical Immunology: Autoimmune Diseases; ; Mackay, I.R.; Rose, N.R.; Diamond, B.; Davidson, A. Eds.. Springer New York: New York, NY, 2014, pp. 141-146.
[http://dx.doi.org/10.1007/978-0-387-84828-0_201]
[18]
Miller, S.A.; Dykes, D.D.; Polesky, H.F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res., 1988, 16(3), 1215.
[http://dx.doi.org/10.1093/nar/16.3.1215] [PMID: 3344216]
[19]
Lim, A.Kh. Diabetic nephropathy - complications and treatment. Int. J. Nephrol. Renovasc. Dis., 2014, 7, 361-381.
[http://dx.doi.org/10.2147/IJNRD.S40172] [PMID: 25342915]
[20]
Freedman, B.I.; Bostrom, M.; Daeihagh, P.; Bowden, D.W. Genetic factors in diabetic nephropathy. Clin. J. Am. Soc. Nephrol., 2007, 2(6), 1306-1316.
[http://dx.doi.org/10.2215/CJN.02560607] [PMID: 17942768]
[21]
Watts, G.F.; Taub, N.; Gant, V.; Wilson, I.; Shaw, K.M. The immunogenetics of early nephropathy in insulin-dependent diabetes mellitus: association between the HLA-A2 antigen and albuminuria. Q. J. Med., 1992, 83(302), 461-471.
[PMID: 1448547]
[22]
Chowdhury, T.A.; Dyer, P.H.; Mijovic, C.H.; Dunger, D.B.; Barnett, A.H.; Bain, S.C. Human leucocyte antigen and insulin gene regions and nephropathy in type I diabetes. Diabetologia, 1999, 42(8), 1017-1020.
[http://dx.doi.org/10.1007/s001250051262] [PMID: 10491764]
[23]
Freedman, B.I.; Espeland, M.A.; Heise, E.R.; Evans, J.; Canzanello, V.J. Racial variation in human leukocyte antigen frequency in insulin-dependent diabetic nephropathy. J. Am. Soc. Nephrol., 1993, 3(8), 1467-1473.
[PMID: 8490118]
[24]
Tait, B.D.; Colman, P.G.; Morahan, G.; Marchinovska, L.; Dore, E.; Gellert, S.; Honeyman, M.C.; Stephen, K.; Loth, A. HLA genes associated with autoimmunity and progression to disease in type 1 diabetes. Tissue Antigens, 2003, 61(2), 146-153.
[http://dx.doi.org/10.1034/j.1399-0039.2003.00013.x] [PMID: 12694582]
[25]
Rivera, P.S.; Márquez, G.; Cipriani, A.M.; Hassanhi, M.; Villalobos, C.C.; Fuenmayor, A.; Chavez, M.; Montiel, M. HLA class I association with progression to end-stage renal disease in patients from Zulia, Venezuela. Inmunologia, 2012, 31(2), 37-42.
[http://dx.doi.org/10.1016/j.inmuno.2011.12.001]
[26]
Kaya, T. Genetics of Behçet Disease. Pathology Research Internation-al 2012 2012.
[27]
Zhang, Y.; Peng, Y.; Yan, H.; Xu, K.; Saito, M.; Wu, H.; Chen, X.; Ranasinghe, S.; Kuse, N.; Powell, T.; Zhao, Y.; Li, W.; Zhang, X.; Feng, X.; Li, N.; Leligdowicz, A.; Xu, X.; John, M.; Takiguchi, M.; McMichael, A.; Rowland-Jones, S.; Dong, T. Multilayered defense in HLA-B51-associated HIV viral control. J. Immunol., 2011, 187(2), 684-691.
[http://dx.doi.org/10.4049/jimmunol.1100316] [PMID: 21670313]
[28]
Giza, M.; Koftori, D.; Chen, L.; Bowness, P. Is Behçet’s disease a ‘class 1-opathy’? The role of HLA-B*51 in the pathogenesis of Behçet’s disease. Clin. Exp. Immunol., 2018, 191(1), 11-18.
[http://dx.doi.org/10.1111/cei.13049] [PMID: 28898393]
[29]
Svejgaard, A.; Jakobsen, B.K.; Platz, P.; Ryder, L.P.; Nerup, J.; Christy, M.; Borch-Johnsen, K.; Parving, H.H.; Deckert, T.; Mølsted-Pedersen, L. HLA associations in insulin-dependent diabetes: search for heterogeneity in different groups of patients from a homogeneous population. Tissue Antigens, 1986, 28(4), 237-244.
[http://dx.doi.org/10.1111/j.1399-0039.1986.tb00489.x] [PMID: 3492782]
[30]
Cordovado, S.K.; Zhao, Y.; Warram, J.H.; Gong, H.; Anderson, K.L.; Hendrix, M.M.; Hancock, L.N.; Cleary, P.A.; Mueller, P.W. Nephropathy in type 1 diabetes is diminished in carriers of HLA-DRB1*04: the genetics of kidneys in diabetes (GoKinD) study. Diabetes, 2008, 57(2), 518-522.
[http://dx.doi.org/10.2337/db07-0826] [PMID: 18039812]
[31]
Dornan, T.L.; Ting, A.; McPherson, C.K.; Peckar, C.O.; Mann, J.I.; Turner, R.C.; Morris, P.J. Genetic susceptibility to the development of retinopathy in insulin-dependent diabetics. Diabetes, 1982, 31(3), 226-231.
[http://dx.doi.org/10.2337/diab.31.3.226] [PMID: 6818073]
[32]
Raache, R.; Hennachi, R.; Amroune, H.; Heniche, A.; Belanteur, K.; Benyahia, A.; Ouandjeli, K. S.; Barar, A.; Houhou, D.; Mimouni, S.; Gervais, T.; Latinne, D.; Boudiba, A.; Attal, N.; Abbadi, M. C. Gènes de susceptibilité HLA et rétinopathie diabétique chez la population algérienne. journal français d'ophtalmologie, , 2013, 36(3), 247-254.
[33]
Saraheimo, M.; Teppo, A.M.; Forsblom, C.; Fagerudd, J.; Groop, P.H. Diabetic nephropathy is associated with low-grade inflammation in Type 1 diabetic patients. Diabetologia, 2003, 46(10), 1402-1407.
[http://dx.doi.org/10.1007/s00125-003-1194-5] [PMID: 12928771]
[34]
Nayak, R.; Attawia, M.; Eisenbarth, G.; King, G. Are anti-glomerular antibodies associated with diabetic nephropathy? J. Autoimmun., 1990, 3(1), 83.
[http://dx.doi.org/10.1016/0896-8411(90)90084-6]
[35]
Baydanoff, S.; Konova, E.; Ivanova, N. Determination of anti-AGE antibodies in human serum. Glycoconj. J., 1996, 13(3), 335-339.
[http://dx.doi.org/10.1007/BF00731464] [PMID: 8781962]
[36]
Cesbron Gautier, A.; Gagne, K.; Retière, C.; Devys, A.; Bignon, J.; Système, HLA. EMC Hematologie, 2007.
[37]
Duran-Salgado, M.B.; Rubio-Guerra, A.F. Diabetic nephropathy and inflammation. World J. Diabetes, 2014, 5(3), 393-398.
[http://dx.doi.org/10.4239/wjd.v5.i3.393] [PMID: 24936261]
[38]
Moriya, R.; Manivel, J.C.; Mauer, M. Juxtaglomerular apparatus T-cell infiltration affects glomerular structure in Type 1 diabetic patients. Diabetologia, 2004, 47(1), 82-88.
[http://dx.doi.org/10.1007/s00125-003-1253-y] [PMID: 14618232]
[39]
Razanskaite-Virbickiene, D.; Danyte, E.; Zalinkevicius, R. DRB1*03 as a risk factor for microalbuminuria in same dura-tion of type 1 diabetes: a case control study. BMC Nephrol, 2016, 17(38), 016-0252.
[40]
Rønningen, K.S.; Bangstad, H.J.; Undlien, D.E.; Thorsby, E. Influence of genetic factors (HLA class II genes, insulin-gene region polymorphisms) and metabolic control on the development of diabetic nephropathy. Diabetes Res., 1993, 23(1), 31-40.
[PMID: 7924146]
[41]
Walton, C.; Dyer, P.A.; Davidson, J.A.; Harris, R.; Mallick, N.P.; Oleesky, S. HLA antigens and risk factors for nephropathy in type 1 (insulin-dependent) diabetes mellitus. Diabetologia, 1984, 27(1), 3-7.
[http://dx.doi.org/10.1007/BF00253492] [PMID: 6590402]
[42]
Font-Porterias, N.; Solé-Morata, N.; Serra-Vidal, G.; Bekada, A.; Fadhlaoui-Zid, K.; Zalloua, P.; Calafell, F.; Comas, D. The genetic landscape of Mediterranean North African populations through complete mtDNA sequences. Ann. Hum. Biol., 2018, 45(1), 98-104.
[http://dx.doi.org/10.1080/03014460.2017.1413133] [PMID: 29382280]
[43]
Hajjej, A.; Almawi, W.Y.; Arnaiz-Villena, A.; Hattab, L.; Hmida, S. The genetic heterogeneity of Arab populations as inferred from HLA genes. PLoS One, 2018, 13(3)e0192269
[http://dx.doi.org/10.1371/journal.pone.0192269] [PMID: 29522542]
[44]
Eddaikra, A.; Amroun, H.; Raache, R.; Galleze, A.; Abdallah-Elhadj, N.; Azzouz, M.; Meçabih, F.; Mechti, B.; Abbadi, M.C.; Touil-Boukoffa, C.; Attal, N. Clinical variables and ethnicity may influenced by polymorphism of CAT -262C/T and MnSOD 47C/T antioxidant enzymes in Algerian type1 diabetes without complications. Gene, 2018, 670, 182-192.
[http://dx.doi.org/10.1016/j.gene.2018.05.105] [PMID: 29859283]


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VOLUME: 19
ISSUE: 8
Year: 2019
Page: [1157 - 1164]
Pages: 8
DOI: 10.2174/1871530319666190215143059
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