Different DRB1*03:01-DQB1*02:01 haplotypes confer different risk for celiac disease
S Alshiekh1,2, L P Zhao3, Å Lernmark1
1Department of Clinical Sciences, Lund University/CRC, Skåne University Hospital, Malmö, Sweden.
HLA
|June 7, 2017
Summary
This study identifies specific human leukocyte antigen (HLA) haplotypes associated with celiac disease risk, particularly DRB3*01:01:02-DQA1*05:01-DQB1*02:01, which is most significant in Scandinavian populations.
Area of Science:
- Genetics
- Immunology
- Gastroenterology
Background:
- Celiac disease is linked to specific human leukocyte antigen (HLA) haplotypes, including HLA-DR3-DQA1*05:01-DQB1*02:01 and DR4-DQA1*03:01-DQB1*03:02.
- Over 40 non-HLA genetic loci are also associated with celiac disease.
- Previous analyses have explored HLA haplotypes in celiac disease.
Purpose of the Study:
- To extend previous analyses of HLA haplotypes in celiac disease using next-generation targeted sequencing.
- To identify specific HLA class II haplotypes conferring risk for celiac disease.
Main Methods:
- Next-generation targeted sequencing of HLA class II haplotypes (HLA-DRB1, DRB3, DRB4, DRB5, DQA1, DQB1).
- Inclusion of 143 celiac disease patients and 135 non-celiac controls.
- Calculation of odds ratios (RR) for each allele and haplotype frequency.
Main Results:
- The strongest risk haplotype for celiac disease identified was DRB3*01:01:02 in linkage with DQA1*05:01-DQB1*02:01 (RR = 6.34).
- In Scandinavian patients, DRB3*01:01:02-DQA1*05:01-DQB1*02:01 showed the highest significance (RR = 4.63).
- Among non-Scandinavians, DRB1*07:01:01-DRB4*01:03:01-DQA1*02:01-DQB1*02:02:01 presented the highest risk (RR = 7.94).
- Two distinct DR3-DQA1*05:01-DQB*02:01 risk haplotypes were identified, differentiated by DRB3*01:01:02 or DRB3*02:02:01 alleles.
Conclusions:
- Different DRB1*03:01-DQB1*02:01 haplotypes confer varying risks for celiac disease.
- The risk haplotype DR3-DRB3*01:01:02-DQA1*05:01-DQB1*02:01 is predominant in celiac disease patients of Scandinavian ethnicity.
More Related Videos
Related Concept Videos
Genome-wide Association Studies-GWAS
16.0K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
16.0K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
56
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
56
Blood Types
23.5K
Human blood is classified into different types based on the presence of antigens on the red blood cell's surface and antibodies in the plasma. Proper identification of blood type is essential for successful blood transfusion. The International Society of Blood Transfusion has identified 38 human blood types based on the surface antigens on the red blood cells. The most common types are ABO, Rh, and MNS blood types.
ABO blood group
ABO antigens are glycoproteins encoded by genes present on...
ABO blood group
ABO antigens are glycoproteins encoded by genes present on...
23.5K
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
65
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
65
Genetic Lingo
116.2K
Overview
116.2K
Multiple Allele Traits
38.4K
The Concept of Multiple Allelism
38.4K


