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Association of HLA‐DR‐DQ alleles, haplotypes, and diplotypes with type 1 diabetes in Saudis
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AbstractAimsType 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.MethodsA 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.ResultsDRB1*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.ConclusionsHLA‐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.
Title: Association of HLA‐DR‐DQ alleles, haplotypes, and diplotypes with type 1 diabetes in Saudis
Description:
AbstractAimsType 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.
MethodsA 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.
ResultsDRB1*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.
ConclusionsHLA‐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.
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