Association of HLA-DR-DQ alleles, haplotypes, and diplotypes with type 1 diabetes in Saudis

Nezar Eltayeb-Elsheikh; Eltahir Khalil; Mohamed Mubasher; Abdullah AlJurayyan; Hanan AlHarthi; Waleed H. Omer; Inas Elghazali; Suphia M. Sherbeeni; Mohammed A. Alghofely; Jorma Ilonen; Gehad Elghazali

doi:10.1002/dmrr.3345

Association of HLA-DR-DQ alleles, haplotypes, and diplotypes with type 1 diabetes in Saudis

Nezar Eltayeb-Elsheikh
, Eltahir Khalil
, Mohamed Mubasher
, Abdullah AlJurayyan
, Hanan AlHarthi
, Waleed H. Omer
, Inas Elghazali
, Suphia M. Sherbeeni
, Mohammed A. Alghofely
, Jorma Ilonen
, Gehad Elghazali

King Fahad Medical City
University of Khartoum
Morehouse School of Medicine
Research Organization of Information and Systems, National Institute of Genetics Mishima
Umeå University
University of Turku

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Aims: Type 1 diabetes (T1D) is an autoimmune disease that affects many children worldwide. Genetic factors and environmental triggers play crucial interacting roles in the aetiology. This study aimed to assess the contribution of HLA-DRB1-DQA1-DQB1 alleles, haplotypes, and genotypes to the risk of T1D among Saudis. Methods: A total of 222 children with T1D and 342 controls were genotyped for HLA-DRB1, -DQA1, and -DQB1 using reverse sequence-specific oligonucleotide (rSSO) Lab Type high definition (HD) kits. Alleles, haplotypes, and diplotypes were compared between cases and controls using the SAS statistical package. Results: DRB1*03:01-DQA1*05:01-DQB1*02:01 (32.4%; OR = 3.68; P_c <.0001), DRB1*04:05-DQA1*03:02-DQB1*03:02 (6.6%; OR = 6.76; P_c <.0001), DRB1*04:02-DQA1*03:01-DQB1*03:02 (6.0%; OR = 3.10; P_c =.0194), DRB1*04:01-DQA1*03:01-DQB1*03:02 (3.7%; OR = 4.22; P_c =.0335), and DRB1*04:05-DQA1*03:02-DQB1*02:02 (2.7%; OR = 6.31; P_c =.0326) haplotypes were significantly increased in cases compared to controls, whereas DRB1*07:01-DQA1*02:01-DQB1*02:02 (OR = 0.41; P_c =.0001), DRB1*13:01-DQA1*01:03-DQB1*06:03 (OR = 0.05; P_c <.0001), DRB1*15:01-DQA1*01:02-DQB1*06:02 (OR = 0.03; P_c <.0001), and DRB1*11:01-DQA1*05:05-DQB1*03:01 (OR = 0.07; P_c =.0291) were significantly decreased. Homozygous DRB1*03:01-DQA1*05:01-DQB1*02:01 genotypes and combinations of DRB1*03:01-DQA1*05:01-DQB1*02:01 with DRB1*04:05-DQA1*03:02-DQB1*03:02, DRB1*04:02-DQA1*03:01-DQB1*03:02, and DRB1*04:01-DQA1*03:01-DQB1*03:02 were significantly increased in cases than controls. Combinations of DRB1*03:01-DQA1*05:01-DQB1*02:01 with DRB1*07:01-DQA1*02:01-DQB1*02:02 and DRB1*13:02-DQA1*01:02-DQB1*06:04 showed low OR values but did not remain significantly decreased after Bonferroni correction. Conclusions: HLA-DRB1-DQA1-DQB1 alleles, haplotypes, and diplotypes in Saudis with T1D are not markedly different from those observed in Western and Middle-Eastern populations but are quite different than those of East Asians.

Original language	English
Article number	e3345
Journal	Diabetes/Metabolism Research and Reviews
Volume	36
Issue number	8
DOIs	https://doi.org/10.1002/dmrr.3345
State	Published - Nov 2020

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

HLA alleles
Saudis
haplotypes
type 1 diabetes

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10.1002/dmrr.3345

Cite this

@article{1b55607067c0418e8706cfe806053202,

title = "Association of HLA-DR-DQ alleles, haplotypes, and diplotypes with type 1 diabetes in Saudis",

abstract = "Aims: Type 1 diabetes (T1D) is an autoimmune disease that affects many children worldwide. Genetic factors and environmental triggers play crucial interacting roles in the aetiology. This study aimed to assess the contribution of HLA-DRB1-DQA1-DQB1 alleles, haplotypes, and genotypes to the risk of T1D among Saudis. Methods: A total of 222 children with T1D and 342 controls were genotyped for HLA-DRB1, -DQA1, and -DQB1 using reverse sequence-specific oligonucleotide (rSSO) Lab Type high definition (HD) kits. Alleles, haplotypes, and diplotypes were compared between cases and controls using the SAS statistical package. Results: DRB1*03:01-DQA1*05:01-DQB1*02:01 (32.4\%; OR = 3.68; Pc <.0001), DRB1*04:05-DQA1*03:02-DQB1*03:02 (6.6\%; OR = 6.76; Pc <.0001), DRB1*04:02-DQA1*03:01-DQB1*03:02 (6.0\%; OR = 3.10; Pc =.0194), DRB1*04:01-DQA1*03:01-DQB1*03:02 (3.7\%; OR = 4.22; Pc =.0335), and DRB1*04:05-DQA1*03:02-DQB1*02:02 (2.7\%; OR = 6.31; Pc =.0326) haplotypes were significantly increased in cases compared to controls, whereas DRB1*07:01-DQA1*02:01-DQB1*02:02 (OR = 0.41; Pc =.0001), DRB1*13:01-DQA1*01:03-DQB1*06:03 (OR = 0.05; Pc <.0001), DRB1*15:01-DQA1*01:02-DQB1*06:02 (OR = 0.03; Pc <.0001), and DRB1*11:01-DQA1*05:05-DQB1*03:01 (OR = 0.07; Pc =.0291) were significantly decreased. Homozygous DRB1*03:01-DQA1*05:01-DQB1*02:01 genotypes and combinations of DRB1*03:01-DQA1*05:01-DQB1*02:01 with DRB1*04:05-DQA1*03:02-DQB1*03:02, DRB1*04:02-DQA1*03:01-DQB1*03:02, and DRB1*04:01-DQA1*03:01-DQB1*03:02 were significantly increased in cases than controls. Combinations of DRB1*03:01-DQA1*05:01-DQB1*02:01 with DRB1*07:01-DQA1*02:01-DQB1*02:02 and DRB1*13:02-DQA1*01:02-DQB1*06:04 showed low OR values but did not remain significantly decreased after Bonferroni correction. Conclusions: HLA-DRB1-DQA1-DQB1 alleles, haplotypes, and diplotypes in Saudis with T1D are not markedly different from those observed in Western and Middle-Eastern populations but are quite different than those of East Asians.",

keywords = "HLA alleles, Saudis, haplotypes, type 1 diabetes",

author = "Nezar Eltayeb-Elsheikh and Eltahir Khalil and Mohamed Mubasher and Abdullah AlJurayyan and Hanan AlHarthi and Omer, \{Waleed H.\} and Inas Elghazali and Sherbeeni, \{Suphia M.\} and Alghofely, \{Mohammed A.\} and Jorma Ilonen and Gehad Elghazali",

note = "Publisher Copyright: {\textcopyright} 2020 John Wiley \& Sons Ltd",

year = "2020",

month = nov,

doi = "10.1002/dmrr.3345",

language = "English",

volume = "36",

journal = "Diabetes/Metabolism Research and Reviews",

issn = "1520-7552",

publisher = "John Wiley and Sons Ltd",

number = "8",

}

TY - JOUR

T1 - Association of HLA-DR-DQ alleles, haplotypes, and diplotypes with type 1 diabetes in Saudis

AU - Eltayeb-Elsheikh, Nezar

AU - Khalil, Eltahir

AU - Mubasher, Mohamed

AU - AlJurayyan, Abdullah

AU - AlHarthi, Hanan

AU - Omer, Waleed H.

AU - Elghazali, Inas

AU - Sherbeeni, Suphia M.

AU - Alghofely, Mohammed A.

AU - Ilonen, Jorma

AU - Elghazali, Gehad

PY - 2020/11

Y1 - 2020/11

N2 - Aims: Type 1 diabetes (T1D) is an autoimmune disease that affects many children worldwide. Genetic factors and environmental triggers play crucial interacting roles in the aetiology. This study aimed to assess the contribution of HLA-DRB1-DQA1-DQB1 alleles, haplotypes, and genotypes to the risk of T1D among Saudis. Methods: A total of 222 children with T1D and 342 controls were genotyped for HLA-DRB1, -DQA1, and -DQB1 using reverse sequence-specific oligonucleotide (rSSO) Lab Type high definition (HD) kits. Alleles, haplotypes, and diplotypes were compared between cases and controls using the SAS statistical package. Results: DRB1*03:01-DQA1*05:01-DQB1*02:01 (32.4%; OR = 3.68; Pc <.0001), DRB1*04:05-DQA1*03:02-DQB1*03:02 (6.6%; OR = 6.76; Pc <.0001), DRB1*04:02-DQA1*03:01-DQB1*03:02 (6.0%; OR = 3.10; Pc =.0194), DRB1*04:01-DQA1*03:01-DQB1*03:02 (3.7%; OR = 4.22; Pc =.0335), and DRB1*04:05-DQA1*03:02-DQB1*02:02 (2.7%; OR = 6.31; Pc =.0326) haplotypes were significantly increased in cases compared to controls, whereas DRB1*07:01-DQA1*02:01-DQB1*02:02 (OR = 0.41; Pc =.0001), DRB1*13:01-DQA1*01:03-DQB1*06:03 (OR = 0.05; Pc <.0001), DRB1*15:01-DQA1*01:02-DQB1*06:02 (OR = 0.03; Pc <.0001), and DRB1*11:01-DQA1*05:05-DQB1*03:01 (OR = 0.07; Pc =.0291) were significantly decreased. Homozygous DRB1*03:01-DQA1*05:01-DQB1*02:01 genotypes and combinations of DRB1*03:01-DQA1*05:01-DQB1*02:01 with DRB1*04:05-DQA1*03:02-DQB1*03:02, DRB1*04:02-DQA1*03:01-DQB1*03:02, and DRB1*04:01-DQA1*03:01-DQB1*03:02 were significantly increased in cases than controls. Combinations of DRB1*03:01-DQA1*05:01-DQB1*02:01 with DRB1*07:01-DQA1*02:01-DQB1*02:02 and DRB1*13:02-DQA1*01:02-DQB1*06:04 showed low OR values but did not remain significantly decreased after Bonferroni correction. Conclusions: HLA-DRB1-DQA1-DQB1 alleles, haplotypes, and diplotypes in Saudis with T1D are not markedly different from those observed in Western and Middle-Eastern populations but are quite different than those of East Asians.

AB - Aims: Type 1 diabetes (T1D) is an autoimmune disease that affects many children worldwide. Genetic factors and environmental triggers play crucial interacting roles in the aetiology. This study aimed to assess the contribution of HLA-DRB1-DQA1-DQB1 alleles, haplotypes, and genotypes to the risk of T1D among Saudis. Methods: A total of 222 children with T1D and 342 controls were genotyped for HLA-DRB1, -DQA1, and -DQB1 using reverse sequence-specific oligonucleotide (rSSO) Lab Type high definition (HD) kits. Alleles, haplotypes, and diplotypes were compared between cases and controls using the SAS statistical package. Results: DRB1*03:01-DQA1*05:01-DQB1*02:01 (32.4%; OR = 3.68; Pc <.0001), DRB1*04:05-DQA1*03:02-DQB1*03:02 (6.6%; OR = 6.76; Pc <.0001), DRB1*04:02-DQA1*03:01-DQB1*03:02 (6.0%; OR = 3.10; Pc =.0194), DRB1*04:01-DQA1*03:01-DQB1*03:02 (3.7%; OR = 4.22; Pc =.0335), and DRB1*04:05-DQA1*03:02-DQB1*02:02 (2.7%; OR = 6.31; Pc =.0326) haplotypes were significantly increased in cases compared to controls, whereas DRB1*07:01-DQA1*02:01-DQB1*02:02 (OR = 0.41; Pc =.0001), DRB1*13:01-DQA1*01:03-DQB1*06:03 (OR = 0.05; Pc <.0001), DRB1*15:01-DQA1*01:02-DQB1*06:02 (OR = 0.03; Pc <.0001), and DRB1*11:01-DQA1*05:05-DQB1*03:01 (OR = 0.07; Pc =.0291) were significantly decreased. Homozygous DRB1*03:01-DQA1*05:01-DQB1*02:01 genotypes and combinations of DRB1*03:01-DQA1*05:01-DQB1*02:01 with DRB1*04:05-DQA1*03:02-DQB1*03:02, DRB1*04:02-DQA1*03:01-DQB1*03:02, and DRB1*04:01-DQA1*03:01-DQB1*03:02 were significantly increased in cases than controls. Combinations of DRB1*03:01-DQA1*05:01-DQB1*02:01 with DRB1*07:01-DQA1*02:01-DQB1*02:02 and DRB1*13:02-DQA1*01:02-DQB1*06:04 showed low OR values but did not remain significantly decreased after Bonferroni correction. Conclusions: HLA-DRB1-DQA1-DQB1 alleles, haplotypes, and diplotypes in Saudis with T1D are not markedly different from those observed in Western and Middle-Eastern populations but are quite different than those of East Asians.

KW - HLA alleles

KW - Saudis

KW - haplotypes

KW - type 1 diabetes

UR - https://www.scopus.com/pages/publications/85086378317

U2 - 10.1002/dmrr.3345

DO - 10.1002/dmrr.3345

M3 - Article

C2 - 32418312

AN - SCOPUS:85086378317

SN - 1520-7552

VL - 36

JO - Diabetes/Metabolism Research and Reviews

JF - Diabetes/Metabolism Research and Reviews

IS - 8

M1 - e3345

ER -

Association of HLA-DR-DQ alleles, haplotypes, and diplotypes with type 1 diabetes in Saudis

Abstract

UN SDGs

Keywords

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