Sequencing-based genotyping and association analysis of the MICA and MICB genes in type 1 diabetes

Sarah F Field, Sergey Nejentsev, Neil M Walker, Joanna M M Howson, Lisa M Godfrey, Jennifer D Jolley, Matthew P A Hardy, John A Todd

Research output: Contribution to journalArticleAcademicpeer-review

34 Citations (Scopus)


OBJECTIVE: The nonclassical major histocompatibility complex (MHC) class I chain-related molecules (MICs), encoded within the MHC, function in immunity. The transmembrane polymorphism in MICA (MICA-STR) has been reported to be associated with type 1 diabetes. In this study, we directly sequenced both of the highly polymorphic MIC genes (MICA and MICB) in order to establish whether they are associated with type 1 diabetes independently of the known type 1 diabetes MHC class II genes HLA-DRB1 and HLA-DQB1.

RESEARCH DESIGN AND METHODS: We developed a sequencing-based typing method and genotyped MICA and MICB in 818 families (2,944 individuals) with type 1 diabetes from the U.K. and U.S. (constructing the genotype from single nucleotide polymorphisms in exons 2-4 of MICA and 2-5 of MICB) and additionally genotyped the MICA-STR in 2,023 type 1 diabetic case subjects and 1,748 control subjects from the U.K. We analyzed the association of the MICA and MICB alleles and genotypes with type 1 diabetes using regression methods.

RESULTS: We identified known MICA and MICB alleles and discovered four new MICB alleles. Based on this large-scale and detailed genotype data, we found no evidence for association of MICA and MICB with type 1 diabetes independently of the MHC class II genes (MICA P = 0.08, MICA-STR P = 0.76, MICB P = 0.03, after conditioning on HLA-DRB1 and HLA-DQB1).

CONCLUSIONS: Common MICA and MICB genetic variations including the MICA-STR are not associated, in a primary way, with susceptibility to type 1 diabetes.

Original languageEnglish
Pages (from-to)1753-6
Number of pages4
Issue number6
Publication statusPublished - Jun 2008
Externally publishedYes


  • Amino Acid Substitution
  • Diabetes Mellitus, Type 1/genetics
  • Exons
  • Genetic Predisposition to Disease
  • Genotype
  • HLA-D Antigens/genetics
  • HLA-DQ Antigens/genetics
  • HLA-DQ beta-Chains
  • HLA-DR Antigens/genetics
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class I/genetics
  • Humans
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide
  • Reference Values

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