Association of HLA-DRB1 and -DQ Alleles and Haplotypes with Type 1 Diabetes in Jordanians

Page: [895 - 902] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

Background: The Human Leukocyte Antigen (HLA) class II genes, particularly the HLADR and -DQ loci, have been shown to play a crucial role in Type 1 Diabetes (T1D) development.

Objective: This study is the first to examine the contribution of the HLA-DR/DQ alleles and haplotypes to T1D susceptibility in Jordanians.

Methods: Polymerase chain reaction sequence-specific primers (PCR-SSP) were used to genotype 41 Jordanian healthy controls and 50 insulin-dependent diabetes mellitus (IDDM) patients.

Results: The following alleles were found to be significant high risk alleles in T1D Jordanian patients: DRB1*04 (OR=3.95, p<0.001), DRB1*0301(OR=5.27, p<0.001), DQA1*0301 (OR=5.67, p<0.001), DQA1*0501(OR=3.18, p=0.002), DQB1*0201(OR=2.18, p=0.03), DQB1*0302 (OR=5.67, p<0.001). However, Jordanians harboring the DRB1*0701 (OR=0.37, p=0.01), DRB1*1101 (OR=0.2, p=0.01), DQA1*0505 (OR=0.31, p=0.02), DQA1*0103 (OR=0.33, p=0.04), DQA1*0201 (OR=0.45, p=0.04), DQB1*0301 (OR=0.23, p=0.001), DQB1*0501 (OR=0.18, p=0.009) alleles had a significantly lower risk of developing T1D.

Conclusion: A strong positive association of DRB1*04-DQA1*0301-DQBl*0302 (OR=5.67, p<0.001) and DRB1*0301-DQA1*0501-DQB1*0201 (OR=6.24, p<0.001) putative haplotypes with IDDM was evident in Jordanian IDDM patients whereas DRB1*1101-DQA1*0505- DQB1*0301 (OR=0.23, p=0.03) was shown to have a protective role against T1D in Jordanians. Our findings show that specific HLA class II alleles and haplotypes are significantly associated with susceptibility to T1D in Jordanians.

Keywords: Insulin-dependent diabetes mellitus (IDDM), Type 1 diabetes mellitus (T1D), HLA-DRB1, HLA-DQA1, HLADQB1, Jordanians.

Graphical Abstract

[1]
Pociot, F.; Lernmark, Å. Genetic risk factors for type 1 diabetes. Lancet, 2016, 387(10035), 2331-2339.
[http://dx.doi.org/10.1016/S0140-6736(16)30582-7] [PMID: 27302272]
[2]
Wang, Z.; Xie, Z.; Lu, Q.; Chang, C.; Zhou, Z. Beyond Genetics: What Causes Type 1 Diabetes. Clin. Rev. Allergy Immunol., 2017, 52(2), 273-286.
[http://dx.doi.org/10.1007/s12016-016-8592-1] [PMID: 27878451]
[3]
Maahs, D.M.; West, N.A.; Lawrence, J.M.; Mayer-Davis, E.J. Epidemiology of type 1 diabetes. Endocrinol. Metab. Clin. North Am., 2010, 39(3), 481-497.
[http://dx.doi.org/10.1016/j.ecl.2010.05.011] [PMID: 20723815]
[4]
Zayed, H. Genetic Epidemiology of Type 1 Diabetes in the 22 Arab Countries. Curr. Diab. Rep., 2016, 16(5), 37.
[http://dx.doi.org/10.1007/s11892-016-0736-4] [PMID: 26983625]
[5]
Soliman, A.T.; al-Salmi, I.S.; Asfour, M.G. Epidemiology of childhood insulin-dependent diabetes mellitus in the Sultanate of Oman. Diabet. Med., 1996, 13(6), 582-586.
[http://dx.doi.org/10.1002/(SICI)1096-9136(199606)13:6<582::AID-DIA114>3.0.CO;2-E] [PMID: 8799664]
[6]
Habeb, A.M.; Al-Magamsi, M.S.F.; Halabi, S.; Eid, I.M.; Shalaby, S.; Bakoush, O. High incidence of childhood type 1 diabetes in Al-Madinah, North West Saudi Arabia (2004-2009). Pediatr. Diabetes, 2011, 12(8), 676-681.
[http://dx.doi.org/10.1111/j.1399-5448.2011.00765.x] [PMID: 21418457]
[7]
Ajlouni, K.; Qusous, Y.; Khawaldeh, A.K.; Jaddou, H.; Batiehah, A.; Ammari, F.; Zaheri, M.; Mashal, A. Incidence of insulin-dependent diabetes mellitus in Jordanian children aged 0-14 y during 1992-1996. Acta Paediatr. , 1999, 88(427), 11-13.
[http://dx.doi.org/10.1111/j.1651-2227.1999.tb14334.x] [PMID: 10195848]
[8]
Kukreja, A.; Cost, G.; Marker, J.; Zhang, C.; Sun, Z.; Lin-Su, K.; Ten, S.; Sanz, M.; Exley, M.; Wilson, B.; Porcelli, S.; Maclaren, N. Multiple immuno-regulatory defects in type-1 diabetes. J. Clin. Invest., 2002, 109(1), 131-140.
[http://dx.doi.org/10.1172/JCI0213605] [PMID: 11781358]
[9]
Todd, J.A.; Walker, N.M.; Cooper, J.D.; Smyth, D.J.; Downes, K.; Plagnol, V.; Bailey, R.; Nejentsev, S.; Field, S.F.; Payne, F.; Lowe, C.E.; Szeszko, J.S.; Hafler, J.P.; Zeitels, L.; Yang, J.H.M.; Vella, A.; Nutland, S.; Stevens, H.E.; Schuilenburg, H.; Coleman, G.; Maisuria, M.; Meadows, W.; Smink, L.J.; Healy, B.; Burren, O.S.; Lam, A.A.C.; Ovington, N.R.; Allen, J.; Adlem, E.; Leung, H.T.; Wallace, C.; Howson, J.M.M.; Guja, C.; Ionescu-Tîrgovişte, C.; Simmonds, M.J.; Heward, J.M.; Gough, S.C.L.; Dunger, D.B.; Wicker, L.S.; Clayton, D.G. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat. Genet., 2007, 39(7), 857-864.
[http://dx.doi.org/10.1038/ng2068] [PMID: 17554260]
[10]
Howson, J.M.M.; Stevens, H.; Smyth, D.J.; Walker, N.M.; Chandler, K.A.; Bingley, P.J.; Todd, J.A. Evidence that HLA class I and II associations with type 1 diabetes, autoantibodies to GAD and autoantibodies to IA-2, are distinct. Diabetes, 2011, 60(10), 2635-2644.
[http://dx.doi.org/10.2337/db11-0131] [PMID: 21831970]
[11]
She, J-X.; Marron, M.P. Genetic susceptibility factors in type 1 diabetes: linkage, disequilibrium and functional analyses. Curr. Opin. Immunol., 1998, 10(6), 682-689.
[http://dx.doi.org/10.1016/S0952-7915(98)80089-7] [PMID: 9914216]
[12]
Gough, S.C.L.; Simmonds, M.J. The HLA Region and Autoimmune Disease: Associations and Mechanisms of Action. Curr. Genomics, 2007, 8(7), 453-465.
[http://dx.doi.org/10.2174/138920207783591690] [PMID: 19412418]
[13]
Cordell, H.J.; Clayton, D.G. A unified stepwise regression procedure for evaluating the relative effects of polymorphisms within a gene using case/control or family data: application to HLA in type 1 diabetes. Am. J. Hum. Genet., 2002, 70(1), 124-141.
[http://dx.doi.org/10.1086/338007] [PMID: 11719900]
[14]
Saruhan-Direskeneli, G.; Uyar, F.A.; Bas, F.; Günöz, H.; Bundak, R.; Saka, N.; Darendeliler, F. HLA-DR and -DQ associations with insulin-dependent diabetes mellitus in a population of Turkey. Hum. Immunol., 2000, 61(3), 296-302.
[http://dx.doi.org/10.1016/S0198-8859(99)00182-2] [PMID: 10689119]
[15]
Hamzeh, A.R.; Nair, P.; Al-Khaja, N.; Al Ali, M.T. Association of HLA-DQA1 and -DQB1 alleles with type I diabetes in Arabs: a meta-analyses. Tissue Antigens, 2015, 86(1), 21-27.
[http://dx.doi.org/10.1111/tan.12598] [PMID: 26095634]
[16]
Hamzeh, A.R.; Nair, P.; Al Ali, M.T. The profile of HLA-DRB1 alleles in Arabs with type 1 diabetes; meta-analyses. HLA, 2016, 87(1), 25-30.
[http://dx.doi.org/10.1111/tan.12717] [PMID: 26818122]
[17]
Khalil, I.; Spyropoulou, M.; Mallet, C.; Loste, M.N.; Douay, C.; Laperrière, J.; Bartzokas, C.; Lepage, V.; Charron, D.; Stavropoulos, C. HLA class II polymorphism and IDDM susceptibility in the Greek population. Eur. J. Immunogenet., 1993, 20(3), 193-199.
[http://dx.doi.org/10.1111/j.1744-313X.1993.tb00110.x] [PMID: 8338816]
[18]
Erlich, H.; Valdes, A.M.; Noble, J.; Carlson, J.A.; Varney, M.; Concannon, P.; Mychaleckyj, J.C.; Todd, J.A.; Bonella, P.; Fear, A.L.; Lavant, E.; Louey, A.; Moonsamy, P. Type 1 Diabetes Genetics Consortium. HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: Analysis of the type 1 diabetes genetics consortium families. Diabetes, 2008, 57(4), 1084-1092.
[http://dx.doi.org/10.2337/db07-1331] [PMID: 18252895]
[19]
World Medical Association. World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA, 2013, 310(20), 2191-2194.
[http://dx.doi.org/10.1001/jama.2013.281053] [PMID: 24141714]
[20]
Elbjeirami, W.M.; Abdel-Rahman, F.; Hussein, A.A. Probability of finding an HLA-matched donor in immediate and extended families: The Jordanian experience. Biol. Blood Marrow Transplant., 2013, 19(2), 221-226.
[http://dx.doi.org/10.1016/j.bbmt.2012.09.009] [PMID: 23025986]
[21]
Szumilas, M. Explaining odds ratios. J. Can. Acad. Child Adolesc. Psychiatry, 2010, 19(3), 227-229.
[PMID: 20842279]
[22]
Current Topics in Histocompatibility and Transplantation. Available at:. http://www.ctht.info/resourceslinks.htm http://www.ctht. info/resourceslinks.htm (Accessed on August 1, 2019).
[23]
Sánchez-Velasco, P.; Karadsheh, N.S.; García-Martín, A.; Ruíz de Alegría, C.; Leyva-Cobián, F. Molecular analysis of HLA allelic frequencies and haplotypes in Jordanians and comparison with other related populations. Hum. Immunol., 2001, 62(9), 901-909.
[http://dx.doi.org/10.1016/S0198-8859(01)00289-0] [PMID: 11543892]
[24]
Petrone, A.; Bugawan, T.L.; Mesturino, C.A.; Nisticò, L.; Galgani, A.; Giorgi, G.; Cascino, I.; Erlich, H.A.; Di Mario, U.; Buzzetti, R. The distribution of HLA class II susceptible/protective haplotypes could partially explain the low incidence of type 1 diabetes in continental Italy (Lazio region). Tissue Antigens, 2001, 58(6), 385-394.
[http://dx.doi.org/10.1034/j.1399-0039.2001.580607.x] [PMID: 11929589]
[25]
Manan, H.; Angham, A.M.; Sitelbanat, A. Genetic and diabetic auto-antibody markers in Saudi children with type 1 diabetes. Hum. Immunol., 2010, 71(12), 1238-1242.
[http://dx.doi.org/10.1016/j.humimm.2010.09.008] [PMID: 20858521]
[26]
Djoulah, S.; Khalil, I.; Beressi, J.P.; Benhamamouch, S.; Bessaoud, K.; Deschamps, I.; Degos, L.; Hors, J. The HLA-DRB1*0405 haplotype is most strongly associated with IDDM in Algerians. Eur. J. Immunogenet., 1992, 19(6), 381-389.
[http://dx.doi.org/10.1111/j.1744-313X.1992.tb00081.x] [PMID: 1477090]
[27]
Kwon, O.J.; Brautbar, C.; Weintrob, N.; Sprecher, E.; Saphirman, C.; Bloch, K.; Pinhas-Hamiel, O.; Assah, S.; Vardi, P.; Israel, S. Immunogenetics of HLA class II in Israeli Ashkenazi Jewish, Israeli non-Ashkenazi Jewish, and in Israeli Arab IDDM patients. Hum. Immunol., 2001, 62(1), 85-91.
[http://dx.doi.org/10.1016/S0198-8859(00)00231-7] [PMID: 11165718]
[28]
Kamoun, H.A.; Hmida, S.; Kaabi, H.; Abid, A.; Slimane Houissa, H.; Maamar, M.; Mojaat, N.; Ben Hamed, L.; Dridi, A.; Kamoun Zribi, M.; Nagati, K.; Haddad, A.; Boukef, K. HLA polymorphism in type 1 diabetes Tunisians. Ann. Genet., 2002, 45(1), 45-50.
[http://dx.doi.org/10.1016/S0003-3995(02)01104-8] [PMID: 11934390]
[29]
Stayoussef, M.; Benmansour, J.; Al-Irhayim, A.Q.; Said, H.B.; Rayana, C.B.; Mahjoub, T.; Almawi, W.Y. Autoimmune type 1 diabetes genetic susceptibility encoded by human leukocyte antigen DRB1 and DQB1 genes in Tunisia. Clin. Vaccine Immunol., 2009, 16(8), 1146-1150.
[http://dx.doi.org/10.1128/CVI.00105-09] [PMID: 19553558]
[30]
Tadmouri, G.O.; Nair, P.; Obeid, T.; Al Ali, M.T.; Al Khaja, N.; Hamamy, H.A. Consanguinity and reproductive health among Arabs. Reprod. Health, 2009, 6(1), 17.
[http://dx.doi.org/10.1186/1742-4755-6-17] [PMID: 19811666]
[31]
Hamamy, H.; Jamhawi, L.; Al-Darawsheh, J.; Ajlouni, K. Consanguineous marriages in Jordan: Why is the rate changing with time? Clin. Genet., 2005, 67(6), 511-516.
[http://dx.doi.org/10.1111/j.1399-0004.2005.00426.x] [PMID: 15857418]
[32]
Al-Jenaidi, F.A.; Wakim-Ghorayeb, S.F.; Al-Abbasi, A.; Arekat, M.R.; Irani-Hakime, N.; Najm, P.; Al-Ola, K.; Motala, A.A.; Almawi, W.Y. Contribution of selective HLA-DRB1/DQB1 alleles and haplotypes to the genetic susceptibility of type 1 diabetes among Lebanese and Bahraini Arabs. J. Clin. Endocrinol. Metab., 2005, 90(9), 5104-5109.
[http://dx.doi.org/10.1210/jc.2005-1166] [PMID: 15985473]
[33]
Al-Harbi, E.M.; Abbassi, A-J.; Tamim, H.; al-Jenaidi, F.; Kooheji, M.; Kamal, M.; al-Mahroos, S.; al-Nasir, F.; Motala, A.A.; Almawi, W.Y. Specific HLA-DRB and -DQB alleles and haplotypes confer disease susceptibility or resistance in Bahraini type 1 diabetes patients. Clin. Diagn. Lab. Immunol., 2004, 11(2), 292-296.
[http://dx.doi.org/10.1128/cdli.11.2.292-296.2004] [PMID: 15013978]
[34]
Haider, M.Z.; Shaltout, A.; Alsaeid, K.; Qabazard, M.; Dorman, J. Prevalence of human leukocyte antigen DQA1 and DQB1 alleles in Kuwaiti Arab children with type 1 diabetes mellitus. Clin. Genet., 1999, 56(6), 450-456.
[http://dx.doi.org/10.1034/j.1399-0004.1999.560608.x] [PMID: 10665665]
[35]
Israel, S.; Kwon, O.J.; Weintrob, N.; Sprecher, E.; Bloch, K.; Assa, S.; Brautbar, C.; Vardi, P. HLA class II immunogenetics of IDDM in Yemenite Jews. Hum. Immunol., 1998, 59(11), 728-733.
[http://dx.doi.org/10.1016/S0198-8859(98)00074-3] [PMID: 9796741]
[36]
Izaabel, H.; Garchon, H-J.; Beaurain, G.; Biga, M.; Akhayat, O.; Bach, J.F.; Caillat-Zucman, S. Distribution of HLA class II alleles and haplotypes in insulin-dependent Moroccan diabetics. Hum. Immunol., 1996, 49(2), 137-143.
[http://dx.doi.org/10.1016/0198-8859(96)00104-8] [PMID: 8872168]