The influence of population stratification on genetic markers associated with type 1 diabetes
Carregando...
Citações na Scopus
23
Tipo de produção
article
Data de publicação
2017
Título da Revista
ISSN da Revista
Título do Volume
Editora
NATURE PUBLISHING GROUP
Autores
BRITO, Luciano Abreu
RUIZ, Marcelo Ortega
MATIOLI, Sergio Russo
PASSOS-BUENO, Maria Rita
Citação
SCIENTIFIC REPORTS, v.7, article ID 43513, 10p, 2017
Resumo
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.
Palavras-chave
Referências
- American Diabetes Association, 2015, DIABETES CARE S1, V38
- Bennett ST, 1997, NAT GENET, V17, P350, DOI 10.1038/ng1197-350
- Bottini N, 2004, NAT GENET, V36, P337, DOI 10.1038/ng1323
- Bussab W. O., 1987, ESTATISTICA BASICA
- Mattana TCC, 2014, MEDIAT INFLAMM, DOI 10.1155/2014/694948
- Conover WJ, 1980, PRACTICAL NONPARAMET
- Donner H, 1997, J CLIN ENDOCR METAB, V82, P143, DOI 10.1210/jc.82.1.143
- Eisenbarth G. S., TYPE 1 DIABETES CELL
- Erlich H, 2008, DIABETES, V57, P1084, DOI 10.2337/db07-1331
- Falush D, 2003, GENETICS, V164, P1567
- Gomes MB, 2014, DIABETOL METAB SYNDR, V6, DOI 10.1186/1758-5996-6-67
- Hauache OM, 2005, DIS MARKERS, V21, P139
- Karvonen M, 2000, DIABETES CARE, V23, P1516, DOI 10.2337/diacare.23.10.1516
- Mainardi-Novo DTO, 2013, CLIN EXP IMMUNOL, V172, P16, DOI 10.1111/cei.12030
- Miller SA, 1998, NUCLEIC ACIDS RES, V16, P1215
- Nassir R, 2009, BMC GENET, V10, DOI 10.1186/1471-2156-10-39
- Neter J., 1990, APPL LINEAR STAT MOD
- Noble JA, 2013, DIABETES, V62, P3292, DOI 10.2337/db13-0094
- Pena SDJ, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0017063
- Pritchard JK, 2000, AM J HUM GENET, V67, P170, DOI 10.1086/302959
- Silva Maria Elizabeth Rossi da, 2008, Arq Bras Endocrinol Metabol, V52, P166
- Steck A. K., 2004, ADV EXP MED BIOL, V552, P170
- Thomson G, 2007, TISSUE ANTIGENS, V70, P110, DOI 10.1111/j.1399-0039.2007.00867.x
- Undlien D. E., 1999, DIABETOLOGIA
- Winer BJ., 1971, STAT PRINCIPLES EXPT
- Zhang Q., 2012, DIABETES RES CLIN PR, V97, P446