Genetic ancestry inferred from autosomal and Y chromosome markers and HLA genotypes in Type 1 Diabetes from an admixed Brazilian population

AbstractThis study aimed to investigate the relationship between genetic ancestry inferred from autosomal and Y chromosome markers and HLA genotypes in patients with Type 1 Diabetes from an admixed Brazilian population. Inference of autosomal ancestry; HLA-DRB1, -DQA1 and -DQB1 typifications; and Y chromosome analysis were performed. European autosomal ancestry was about 50%, followed by approximately 25% of African and Native American. The European Y chromosome was predominant. The HLA-DRB1*03 and DRB1*04 alleles presented risk association with T1D. When the Y chromosome was European, DRB1*03 and DRB1*04 homozygote and DRB1*03/DRB1*04 heterozygote genotypes were the most frequent. The results suggest that individuals from Maranhão have a European origin as their major component; and are patrilineal with greater frequency from the R1b haplogroup. The predominance of the HLA-DRB1*03 and DRB1*04 alleles conferring greater risk in our population and being more frequently related to the ancestry of the European Y chromosome suggests that in our population, the risk of T1D can be transmitted by European ancestors of our process miscegenation. However, the Y sample sizes of Africans and Native Americans were small, and further research should be conducted with large mixed sample sizes to clarify this possible association.

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Genetic Ancestry Inferred From Autosomal and Y Chromosome Markers and HLA Genotypes in Type 1 Diabetes From an Admixed Brazilian Population.

10.21203/rs.3.rs-262854/v1 ◽

2021 ◽

Author(s):

Rossana Santiago de Sousa Azulay ◽

Luís Cristóvão Porto ◽

Dayse Aparecida Silva ◽

Maria da Gloria Tavares ◽

Roberta Dualibe ◽

...

Keyword(s):

Type 1 Diabetes ◽

Native American ◽

Native Americans ◽

Y Chromosome ◽

Chromosome Analysis ◽

Brazilian Population ◽

Genetic Ancestry ◽

Sample Sizes ◽

Chromosome Markers

Abstract This study aimed to investigate the relationship between genetic ancestry inferred from autosomal and Y chromosome markers and HLA genotypes in patients with Type 1 Diabetes from an admixed Brazilian population. Inference of autosomal ancestry; HLA-DRB1, -DQA1 and -DQB1 typifications; and Y chromosome analysis were performed. European autosomal ancestry was about 50%, followed by approximately 25% of African and Native American. The European Y chromosome was predominant. The HLA-DRB1* 03 and DRB1* 04 alleles presented risk association with T1D. When the Y chromosome was European, DRB1*03 and DRB1*04 homozygote and DRB1*03/DRB1*04 heterozygote genotypes were the most frequent. The results suggest that individuals from Maranhão have a European origin as their major component; and are patrilineal with greater frequency from the R1b haplogroup. The predominance of the HLA-DRB1* 03 and DRB1* 04 alleles conferring greater risk in our population and being more frequently related to the ancestry of the European Y chromosome suggests that in our population, the risk of T1D can be transmitted by European ancestors of our process miscegenation. However, the Y sample sizes of Africans and Native Americans were small, and further research should be conducted with large mixed sample sizes to clarify this possible association.

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Children developing type 1 diabetes before 6 years of age have increased linear growth independent of HLA genotypes

Diabetologia ◽

10.1007/s00125-008-1074-0 ◽

2008 ◽

Vol 51 (9) ◽

pp. 1623-1630 ◽

Cited By ~ 40

Author(s):

H. Elding Larsson ◽

G. Hansson ◽

A. Carlsson ◽

E. Cederwall ◽

B. Jonsson ◽

...

Keyword(s):

Type 1 Diabetes ◽

Linear Growth ◽

Hla Genotypes

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Cytotoxic T lymphocyte antigen 4 gene polymorphism confers susceptibility to Type 1 diabetes in Japanese children: analysis of association with HLA genotypes and autoantibodies

Clinical Endocrinology ◽

10.1046/j.1365-2265.2001.01397.x ◽

2001 ◽

Vol 55 (5) ◽

pp. 597-603 ◽

Cited By ~ 19

Author(s):

Noriko Kikuoka ◽

Shigetaka Sugihara ◽

Tatsuo Yanagawa ◽

Ayako Ikezaki ◽

Hye Sook Kim ◽

...

Keyword(s):

Type 1 Diabetes ◽

Gene Polymorphism ◽

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Japanese Children ◽

Lymphocyte Antigen ◽

Hla Genotypes

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Exocrine pancreas function is impaired in adult relatives of patients with type 1 diabetes

Acta Diabetologica ◽

10.1007/s00592-021-01819-2 ◽

2021 ◽

Author(s):

Anna Giovenzana ◽

Federica Vecchio ◽

Federica Cugnata ◽

Alessandro Nonis ◽

Alessandra Mandelli ◽

...

Keyword(s):

At Risk ◽

Type 1 Diabetes ◽

High Risk ◽

Exocrine Pancreas ◽

Pancreatic Enzyme ◽

Low Risk ◽

C Peptide ◽

Hla Genotypes ◽

Pancreas Function

Abstract Aims Alterations of the exocrine pancreas have been reported in type 1 diabetes, but their contribution to the pathogenesis of the disease is poorly understood. Here, we investigated markers of exocrine pancreas dysfunction in individuals at-risk of developing type 1 diabetes. Methods Serum P-amylase and lipase levels were assessed in samples obtained from healthy controls, patients with new onset type 1 diabetes, relatives participating to the TrialNet Pathway to Prevention who were, at blood collection, autoantibody negative or positive for a single autoantibody (low-risk individuals), and positive for multiple autoantibodies (high-risk individuals). Linear mixed models were adopted to estimate variation of pancreatic enzymes among the groups and to evaluate the influence of high-risk HLA genotypes and residual beta cell function on exocrine pancreas function. Results In adults, but not children, reduced levels of P-amylase and lipase were shown in at-risk individuals, including (for P-amylase levels only) those at low-risk, and in T1Dnew. Furthermore, while high-risk HLA genotypes negatively affected P-amylase levels in autoantibody negative adult individuals, fasting C-peptide levels did not correlate with pancreatic enzyme levels. Conclusions Exocrine pancreas dysfunction precedes the onset of type 1 diabetes in adult at-risk individuals and may be unrelated to fasting C-peptide levels.

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High anxiety and depressive symptoms in partners of type 1 diabetes persons in a sample of the Brazilian population

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-020-00531-5 ◽

2020 ◽

Vol 12 (1) ◽

Cited By ~ 1

Author(s):

E. Buin ◽

E. J. Pavin ◽

M. S. V. M. Silveira

Keyword(s):

Type 1 Diabetes ◽

Depressive Symptoms ◽

Brazilian Population ◽

High Anxiety

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P084 Type 1 Diabetes DQA1∼DQB1∼DRB1 haplotypes in an admixed brazilian population

Human Immunology ◽

10.1016/j.humimm.2018.07.143 ◽

2018 ◽

Vol 79 ◽

pp. 123

Author(s):

Luis Cristovao M. Porto ◽

Deborah C. Santos ◽

Leonardo M. Hanhoerster ◽

Aline B. Gabrielli ◽

Juliana P. Motta ◽

...

Keyword(s):

Type 1 Diabetes ◽

Brazilian Population

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HLA Class II Allele Analyses Implicate Common Genetic Components in Type 1 and Non–Insulin-Treated Type 2 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa027 ◽

2020 ◽

Vol 105 (3) ◽

pp. e245-e254 ◽

Cited By ~ 1

Author(s):

Thomas Jacobi ◽

Lucas Massier ◽

Nora Klöting ◽

Katrin Horn ◽

Alexander Schuch ◽

...

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Class Ii ◽

Hla Class Ii ◽

Risk Haplotype ◽

Genetic Components ◽

Hla Genotypes ◽

Increased Risk

Abstract Context Common genetic susceptibility may underlie the frequently observed co-occurrence of type 1 and type 2 diabetes in families. Given the role of HLA class II genes in the pathophysiology of type 1 diabetes, the aim of the present study was to test the association of high density imputed human leukocyte antigen (HLA) genotypes with type 2 diabetes. Objectives and Design Three cohorts (Ntotal = 10 413) from Leipzig, Germany were included in this study: LIFE-Adult (N = 4649), LIFE-Heart (N = 4815) and the Sorbs (N = 949) cohort. Detailed metabolic phenotyping and genome-wide single nucleotide polymorphism (SNP) data were available for all subjects. Using 1000 Genome imputation data, HLA genotypes were imputed on 4-digit level and association tests for type 2 diabetes, and related metabolic traits were conducted. Results In a meta-analysis including all 3 cohorts, the absence of HLA-DRB5 was associated with increased risk of type 2 diabetes (P = 0.001). In contrast, HLA-DQB*06:02 and HLA-DQA*01:02 had a protective effect on type 2 diabetes (P = 0.005 and 0.003, respectively). Both alleles are part of the well-established type 1 diabetes protective haplotype DRB1*15:01~DQA1*01:02~DQB1*06:02, which was also associated with reduced risk of type 2 diabetes (OR 0.84; P = 0.005). On the contrary, the DRB1*07:01~DQA1*02:01~DQB1*03:03 was identified as a risk haplotype in non–insulin-treated diabetes (OR 1.37; P = 0.002). Conclusions Genetic variation in the HLA class II locus exerts risk and protective effects on non–insulin-treated type 2 diabetes. Our data suggest that the genetic architecture of type 1 diabetes and type 2 diabetes might share common components on the HLA class II locus.

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