Abstract
Arka plan/Amaç: Tip
1Diabetes Mellitus (T1DM) bölge, ırk ve etnik kökene göre değişken HLA gen
polimorfizmlerinin sorumlu tutulduğu otoimmün bir hastalıktır. Çoğunlukla DR-DQ
haplotiplerinin çalışıldığı çok sayıda çalışma bulunmasına karşın, sınıf I
HLA-A,B ve C allel ilişkisini araştıran daha az rapor bulunmaktadır. Çalışmanın
amacı T1DM tanılı Türk çocuklarında sınıf I ve II HLA allel dağılımını
araştırmaktır.
Gereç ve Yöntem: 2017-2019 arası tanı
almış 98 (45 kız, 53 erkek) T1DM ve 80 (41 kız, 39 erkek) sağlıklı çocuk HLA
A-B-C ve DQ-DR allelleri açısından tarandı. HLA moleküler analizleri PCR
yöntemi ile çalışıldı. DQ, DR için riskli allel ve haplotipler arasındaki
farkın ölçülmesinde Ki-kare testi kullanıldı ve her değişken için Odds Ratio
(OD) hesaplandı
Bulgular: T1DM’li
çocuklarda en sık saptanan DQ2 (n=60; %61.22) ve DR3 (n=48; %49) idi. DQ3
%34.7(n=34), DR4 %25.5 (n=25) oranında saptandı. HLA I grubunda en sık saptanan
HLA-A2 (n=36; %36.8) ve HLA-A3 (n=26;%26.6) idi. Diğer HLA lokuslarının sıklığı
sırası ile şu şekilde saptandı: HLA-C7 %25.5 (n=25), HLA-C4 %20.4 (n=20)HLA-B8
%18.8 (n=18), HLA-B35 %15.3 (n=15). En sık saptanan haplotipler DRB1*03-DQB1*02, DRB1*04-DQB1*03 ve DRB1*01-DQB1*05 idi. (sırası ile
48(%49), 19(%19.3), 11(%11.2). Kontrol grubu ile karşılaştırıldığında T1DM için
en riskli haplotipler DRB1*03-DQB1*02 (OR;11.84) DRB1*01-DQB1*05 (OR;9.98) ve
DRB1*04-DQB1*02 (OR;5.15) iken en riskli allel grupları ise DQ2 (OR; 7.44) ve
DR3 (OR;6.02) olarak saptandı.
Sonuç: Bu çalışmada T1DM için
en riskli HLA allel grupları ve haplotipleri olarak DR3-DQ2 ve DRB1*03-DQB1*02,
DRB1*04-DQB1*03, DRB1*01-DQB1*05 saptarken HLA-A2/A3, HLA-C7/C4 ve HLA B8/35
allel gruplarının sıklığında artmış bir sıklık saptanmıştır. Bu bulgular, T1DM tanılı Türk çocuklarında HLA sınıf II
HLA DR3-DQ2 allel gruplarındaki artmış sıklık olduğunu ve T1DM ile bazı
allellerinin artmış sıklığı nedeni ile HLA I sınıfı gen bölgeleri arasındaki
ilişkinin de araştırılması gerektiğine işaret etmektedir.
References
- Morahan G, Varney M. The genetics of type 1 diabetes. In The HLA Complex in Biology and Medicine: A Resource Book. Mehra NK, Ed., New Delhi, JayPee Brothers Publishing, 2010, p. 205–218
- Dorman JS1, Bunker CH. HLA-DQ locus of the human leukocyte antigen complex and type 1 diabetes mellitus: a HuGE review. Epidemiol Rev. 2000;22(2):218-27.
- Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 2001;358:221–229.
- Noble JA, Valdes AM. Genetics of the HLA region in the prediction of type 1 diabetes. Curr Diab Rep. 2011 Dec;11(6):533-42.
- Janelle A. Noble and Ana M. Valdes. Genetics of the HLA Region in the Prediction of Type 1 Diabetes. Curr Diab Rep. 2011 Dec; 11(6): 533–542.
- Noble JA, Valdes AM, Varney MD, Carlson JA, et al. HLA class I and genetic susceptibility to type 1 diabetes: results from the Type 1 Diabetes Genetics Consortium. Diabetes. 2010 Nov;59(11):2972-9.
- Barker JM, Triolo TM, Aly TA, et al. Two single nucleotide polymorphisms identify the highest-risk diabetes HLA genotype: potential for rapid screening. Diabetes 2008;57:3152–3155
- Cucca F, Muntoni F, Lampis R, Frau F, et al. Combinations of specific DRB1, DQA1, and DQB1 haplotypes are associated with insulin-dependent diabetes mellitus in Sardinia. Hum Immunol 37:85–94, 1993
- Noble JA, Valdes AM, Cook M, Klitz W, et al.The role of HLA class II genes in insulin-dependent diabetes mellitus: molecular analysis of 180 Caucasian, multiplex families. Am J Hum Genet 59:1134–1148, 1996
- Erlich H, Valdes AM, Noble J, Carlson JA,et al. HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families. Diabetes. 2008 Apr;57(4):1084-92.
- Janelle A. Noble and Henry A. Erlich. Genetics of Type 1 Diabetes. Cold Spring Harb Perspect Med. 2012 Jan; 2(1): a007732.
- Valdes AM, Noble JA, Ge´nin E, Clerget-Darpoux F, et al. Modeling of HLA class II susceptibility to type 1 diabetes reveals an effect associated with DPB1. Genet Epidemiol 21:212–223, 2001
- Michels A, Zhang L, Khadra A, Kushner JA, et al. Prediction and prevention of type 1 diabetes: update on success of prediction and struggles at prevention. Pediatr Diabetes. 2015 Nov;16(7):465-84
- Noble JA, Valdes AM, Bugawan TL, Apple RJ, Thomson G, Erlich HA. The HLA class I A locus affects susceptibility to type 1 diabetes. Hum Immunol 2002;63:657–664
- Noble JA.Immunogenetics of type 1 diabetes: A comprehensive review. J Autoimmun. 2015 Nov;64:101-12.
- Ozsahin H, Haktan M, Ozbakir F, Aydin A, Yazici H. The type 1 diabetes and HLA-DR in Turkey. Diabete Metab. 1991 Jul-Aug;17(4):421-3.
- Mehmet Keskin, Ayşe Aygün, Sacide Pehlivan, Özlem Keskin, et al. Trends in the Frequency of HLA DR-DQ Haplotypes Among Children and Adolescents with Type 1 Diabetes Mellitus in the Southeast Region of Turkey. J Clin Res Pediatr Endocrinol. 2012 Dec; 4(4): 189–192.
- Wu YL, Ding YP, Gao J, Tanaka Y, Zhang W.Risk factors and primary prevention trials for type 1 diabetes.Int J Biol Sci. 2013 Jul 18;9(7):666-79.
- Nguyen C, Varney MD, Harrison LC, Morahan G. Definition of high-risk type 1 diabetes HLA-DR and HLA-DQ types using only three single nucleotide polymorphisms. Diabetes. 2013 Jun;62(6):2135-40.
- Mustafa Soyöz, Burcu Akman, İsmail Totur, Sinem Topçu et al. Human Leukocyte Antigen Class I-II Allele Frequencies and Association Between Human Leukocyte Antigen Alleles and ABO Blood Group Antigens. Turk J Immunol 2016;4(1):14-18.
Abstract
References
- Morahan G, Varney M. The genetics of type 1 diabetes. In The HLA Complex in Biology and Medicine: A Resource Book. Mehra NK, Ed., New Delhi, JayPee Brothers Publishing, 2010, p. 205–218
- Dorman JS1, Bunker CH. HLA-DQ locus of the human leukocyte antigen complex and type 1 diabetes mellitus: a HuGE review. Epidemiol Rev. 2000;22(2):218-27.
- Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 2001;358:221–229.
- Noble JA, Valdes AM. Genetics of the HLA region in the prediction of type 1 diabetes. Curr Diab Rep. 2011 Dec;11(6):533-42.
- Janelle A. Noble and Ana M. Valdes. Genetics of the HLA Region in the Prediction of Type 1 Diabetes. Curr Diab Rep. 2011 Dec; 11(6): 533–542.
- Noble JA, Valdes AM, Varney MD, Carlson JA, et al. HLA class I and genetic susceptibility to type 1 diabetes: results from the Type 1 Diabetes Genetics Consortium. Diabetes. 2010 Nov;59(11):2972-9.
- Barker JM, Triolo TM, Aly TA, et al. Two single nucleotide polymorphisms identify the highest-risk diabetes HLA genotype: potential for rapid screening. Diabetes 2008;57:3152–3155
- Cucca F, Muntoni F, Lampis R, Frau F, et al. Combinations of specific DRB1, DQA1, and DQB1 haplotypes are associated with insulin-dependent diabetes mellitus in Sardinia. Hum Immunol 37:85–94, 1993
- Noble JA, Valdes AM, Cook M, Klitz W, et al.The role of HLA class II genes in insulin-dependent diabetes mellitus: molecular analysis of 180 Caucasian, multiplex families. Am J Hum Genet 59:1134–1148, 1996
- Erlich H, Valdes AM, Noble J, Carlson JA,et al. HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families. Diabetes. 2008 Apr;57(4):1084-92.
- Janelle A. Noble and Henry A. Erlich. Genetics of Type 1 Diabetes. Cold Spring Harb Perspect Med. 2012 Jan; 2(1): a007732.
- Valdes AM, Noble JA, Ge´nin E, Clerget-Darpoux F, et al. Modeling of HLA class II susceptibility to type 1 diabetes reveals an effect associated with DPB1. Genet Epidemiol 21:212–223, 2001
- Michels A, Zhang L, Khadra A, Kushner JA, et al. Prediction and prevention of type 1 diabetes: update on success of prediction and struggles at prevention. Pediatr Diabetes. 2015 Nov;16(7):465-84
- Noble JA, Valdes AM, Bugawan TL, Apple RJ, Thomson G, Erlich HA. The HLA class I A locus affects susceptibility to type 1 diabetes. Hum Immunol 2002;63:657–664
- Noble JA.Immunogenetics of type 1 diabetes: A comprehensive review. J Autoimmun. 2015 Nov;64:101-12.
- Ozsahin H, Haktan M, Ozbakir F, Aydin A, Yazici H. The type 1 diabetes and HLA-DR in Turkey. Diabete Metab. 1991 Jul-Aug;17(4):421-3.
- Mehmet Keskin, Ayşe Aygün, Sacide Pehlivan, Özlem Keskin, et al. Trends in the Frequency of HLA DR-DQ Haplotypes Among Children and Adolescents with Type 1 Diabetes Mellitus in the Southeast Region of Turkey. J Clin Res Pediatr Endocrinol. 2012 Dec; 4(4): 189–192.
- Wu YL, Ding YP, Gao J, Tanaka Y, Zhang W.Risk factors and primary prevention trials for type 1 diabetes.Int J Biol Sci. 2013 Jul 18;9(7):666-79.
- Nguyen C, Varney MD, Harrison LC, Morahan G. Definition of high-risk type 1 diabetes HLA-DR and HLA-DQ types using only three single nucleotide polymorphisms. Diabetes. 2013 Jun;62(6):2135-40.
- Mustafa Soyöz, Burcu Akman, İsmail Totur, Sinem Topçu et al. Human Leukocyte Antigen Class I-II Allele Frequencies and Association Between Human Leukocyte Antigen Alleles and ABO Blood Group Antigens. Turk J Immunol 2016;4(1):14-18.
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Internal Diseases |
| Journal Section | ORIGINAL ARTICLES |
| Authors | |
| Publication Date | December 23, 2019 |
| Submission Date | July 16, 2019 |
| Published in Issue | Year 2019 Volume: 13 Issue: 6 |
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