The influence of population stratification on genetic markers associated with type 1 diabetes

被引：24

作者：

Brasil Gomes, Karla Fabiana ^{[1
]}

Santos, Aritania Sousa ^{[1
]}

Semzezem, Cintia ^{[1
]}

Correia, Marcia Regina ^{[1
]}

Brito, Luciano Abreu ^{[2
]}

Ruiz, Marcelo Ortega ^{[3
]}

Fukui, Rosa Tsuneshiro ^{[1
]}

Matioli, Sergio Russo ^{[2
]}

Passos-Bueno, Maria Rita ^{[2
]}

Rossi da Silva, Maria Elizabeth ^{[1
]}

机构：

[1] Univ Sao Paulo, Hosp Clin, Fac Med, Lab Carboidratos & Radioimunoensaio LIM 18, Av Dr Arnaldo,455 Sala 3324, BR-01246903 Sao Paulo, SP, Brazil

[2] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, Rua Matao 277, BR-05422970 Sao Paulo, SP, Brazil

[3] Immunol Lab, Rua Claudio Manoel Costa,270 Marilia Sao Paulo, Sao Paulo, SP, Brazil

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

SUSCEPTIBILITY;

D O I：

10.1038/srep43513

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Ethnic admixtures may interfere with the definition of type 1 diabetes (T1D) risk determinants. The role of HLA, PTPN22, INS-VNTR, and CTLA4 in T1D predisposition was analyzed in Brazilian T1D patients (n = 915), with 81.7% self-reporting as white and 789 controls (65.6% white). The results were corrected for population stratification by genotyping 93 ancestry informative markers (AIMs) (BeadXpress platform). Ancestry composition and structural association were characterized using Structure 2.3 and STRAT. Ethnic diversity resulted in T1D determinants that were partially discordant from those reported in Caucasians and Africans. The greatest contributor to T1D was the HLA-DR3/DR4 genotype (OR = 16.5) in 23.9% of the patients, followed by -DR3/DR3 (OR = 8.9) in 8.7%, -DR4/DR4 (OR = 4.7) in 6.0% and -DR3/DR9 (OR = 4.9) in 2.6%. Correction by ancestry also confirmed that the DRB1*09DQB1*0202 haplotype conferred susceptibility, whereas the DRB1*07-DQB1*0202 and DRB1*11DQB1*0602 haplotypes were protective, which is similar to reports in African-American patients. By contrast, the DRB1*07-DQB1*0201 haplotype was protective in our population and in Europeans, despite conferring susceptibility to Africans. The DRB1*10-DQB1*0501 haplotype was only protective in the Brazilian population. Predisposition to T1D conferred by PTPN22 and INS-VNTR and protection against T1D conferred by the DRB1*16 allele were confirmed. Correcting for population structure is important to clarify the particular genetic variants that confer susceptibility/protection for T1D in populations with ethnic admixtures.

引用

页数：10

共 26 条

[21] Association mapping in structured populations [J].

Pritchard, JK ;

Stephens, M ;

Rosenberg, NA ;

Donnelly, P .

AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 67 (01) :170-181

[22]

Pugliese A, 2004, ADV EXP MED BIOL, V552, P170

[23]

Silva Maria Elizabeth Rossi da, 2008, Arq Bras Endocrinol Metab, V52, P166, DOI 10.1590/S0004-27302008000200004

[24] Relative predispositional effects of HLA class II DRB1-DQB1 haplotypes and genotypes on type 1 diabetes: a meta-analysis [J].

Thomson, G. ;

Valdes, A. M. ;

Noble, J. A. ;

Kockum, I. ;

Grote, M. N. ;

Najman, J. ;

Erlich, H. A. ;

Cucca, F. ;

Pugliese, A. ;

Steenkiste, A. ;

Dorman, J. S. ;

Caillat-Zucman, S. ;

Hermann, R. ;

Ilonen, J. ;

Lambert, A. P. ;

Bingley, P. J. ;

Gillespie, K. M. ;

Lernmark, A. ;

Sanjeevi, C. B. ;

Ronningen, K. S. ;

Undlien, D. E. ;

Thorsby, E. ;

Petrone, A. ;

Buzzetti, R. ;

Koeleman, B. P. C. ;

Roep, B. O. ;

Saruhan-Direskeneli, G. ;

Uyar, F. A. ;

Gunoz, H. ;

Gorodezky, C. ;

Alaez, C. ;

Boehm, B. O. ;

Mlynarski, W. ;

Ikegami, H. ;

Berrino, M. ;

Fasano, M. E. ;

Dametto, E. ;

Israel, S. ;

Brautbar, C. ;

Santiago-Cortes, A. ;

de Llado, T. Frazer ;

She, J. -X. ;

Bugawan, T. L. ;

Rotter, J. I. ;

Raffel, L. ;

Zeidler, A. ;

Leyva-Cobian, F. ;

Hawkins, B. R. ;

Chan, S. H. ;

Castano, L. .

TISSUE ANTIGENS, 2007, 70 (02) :110-127

[25]

Undlien D. E., 1999, DIABETOLOGIA

[26]

Zhang Q., 2012, DIABETES RES CLIN PR, V97, P446

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