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An investigation of the HLA associations with type 1 Diabetes mellitus and Graves' disease

An investigation of the HLA associations with type 1 Diabetes mellitus and Graves' disease
An investigation of the HLA associations with type 1 Diabetes mellitus and Graves' disease

Type 1 diabetes is associated with certain Human Leucocyte Antigen (HLA) genes. It has been suggested that protection from disease correlates with DQB1 alleles encoding aspartate at position 57 of the DQβ chain. The most consistently postively associated DQA1 allele is DQA1*0301 which is also common in the healthy population. If it is a predisposing allele, its effect must be modified by other factors to distinguish diabetogenic and non-diabetogenic hallotypes. The DR, DQA1 and DQB1 genotypes were determined in 156 Caucasian patients and 116 healthy controls in order to determine those markers associated with susceptibility to and protection from the disease. The promoter region of the DQA1*0301 allele was sequenced in diabetic and control haplotypes to invstigate for disease-specific sequences. The frequency of a disease-associated DQA1*0501 RFLP was determined in patients and controls and the DQA1*0501 promoter region digested with Bgl II to investigate for the presence of a disease-specific restriction site.

These studies demonstrated that DR3 and DR4 haplotypes were associated with Type 1 diabetes, and that DR2, DR6 and DR7 were protective. The Asp57-negative allele, DQB1*0604 was protective which argues against the Asp 57 hypothesis. No DQA1*0301 promoter region polymorphism was found, suggesting that DQA1*0301 does not directly confer suceptibility to disease. The effect of protective HLA markers consistenly dominated over predisposing markers, suggesting that the predominant HLA effect is in protection from Type 1 diabetes.

Graves' disease is associated with DR3 in Caucasians and B46 in the Chinese, particularly in males. HLA genotypes were determined in 66 Chinese Graves' patients and 105 controls to investigate for disease markers common to both Chinese and Caucasian populations and to determine whether there is a sex difference in HLA association in Chinese patients. Tumour necrosis factor-β (TNFB) polymorphism was also investigated in patients and controls.

University of Southampton
Cavan, David Anthony
0f63e12f-9f30-4f6b-a833-e3aaadb0a90b
Cavan, David Anthony
0f63e12f-9f30-4f6b-a833-e3aaadb0a90b

Cavan, David Anthony (1993) An investigation of the HLA associations with type 1 Diabetes mellitus and Graves' disease. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

Type 1 diabetes is associated with certain Human Leucocyte Antigen (HLA) genes. It has been suggested that protection from disease correlates with DQB1 alleles encoding aspartate at position 57 of the DQβ chain. The most consistently postively associated DQA1 allele is DQA1*0301 which is also common in the healthy population. If it is a predisposing allele, its effect must be modified by other factors to distinguish diabetogenic and non-diabetogenic hallotypes. The DR, DQA1 and DQB1 genotypes were determined in 156 Caucasian patients and 116 healthy controls in order to determine those markers associated with susceptibility to and protection from the disease. The promoter region of the DQA1*0301 allele was sequenced in diabetic and control haplotypes to invstigate for disease-specific sequences. The frequency of a disease-associated DQA1*0501 RFLP was determined in patients and controls and the DQA1*0501 promoter region digested with Bgl II to investigate for the presence of a disease-specific restriction site.

These studies demonstrated that DR3 and DR4 haplotypes were associated with Type 1 diabetes, and that DR2, DR6 and DR7 were protective. The Asp57-negative allele, DQB1*0604 was protective which argues against the Asp 57 hypothesis. No DQA1*0301 promoter region polymorphism was found, suggesting that DQA1*0301 does not directly confer suceptibility to disease. The effect of protective HLA markers consistenly dominated over predisposing markers, suggesting that the predominant HLA effect is in protection from Type 1 diabetes.

Graves' disease is associated with DR3 in Caucasians and B46 in the Chinese, particularly in males. HLA genotypes were determined in 66 Chinese Graves' patients and 105 controls to investigate for disease markers common to both Chinese and Caucasian populations and to determine whether there is a sex difference in HLA association in Chinese patients. Tumour necrosis factor-β (TNFB) polymorphism was also investigated in patients and controls.

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Published date: 1993

Identifiers

Local EPrints ID: 462381
URI: http://eprints.soton.ac.uk/id/eprint/462381
PURE UUID: 67c583ca-2459-480e-9bfe-6fce96480462

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Date deposited: 04 Jul 2022 19:06
Last modified: 23 Jul 2022 01:07

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Contributors

Author: David Anthony Cavan

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