Sequencing-based genotyping and association analysis of the MICA and MICB genes in type 1 diabetes.
نویسندگان
چکیده
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.
منابع مشابه
MMP9 Promoter Polymorphism (-1562 C/T) Does not Affect the Serum Levels of Soluble MICB and MICA in Breast Cancer
Background: The role of Matrix Metalloproteinase 9 (MMP9) in tumor invasion and progression is prominent. A single nucleotide polymorphism (SNP) in the promoter region of MMP9 (-1562 C/T) increases the transcription and expression of this gene. On the other hand, MHC class I chain-related protein A and B (MICA/B) in soluble forms may impair tumor immunogenicity by reducing Natural Killer Group ...
متن کاملAqueous Humor and Serum Concentrations of Soluble MICA and MICB in Glaucoma Patients
Background: Immune reactions have been reported to be involved in the destruction of retinal ganglion cells (RGCs) in glaucoma. Objective: To investigate the role of major histocompatibility complex class I-related chain A and B (MICA and MICB) molecules in the pathogenesis of glaucoma. Methods: Aqueous humor and serum samples from 15 glaucoma patients and 45 patients with cataract, undergoing ...
متن کاملASSOCIATION ANALYSIS BETWEEN RS10830962 VARIANT OF MTNR1B GENE AND TYPE 2 DIABETES MELLITUS RISK
Background: Type 2 diabetes mellitus (T2DM) is the most common type of diabetes that was classically characterized by pancreatic β-cell dysfunction. Changes in circadian patterns is one of the reasons which can increase the occurrence of diabetes. Melatonin is one of the biological molecules which plays an important role in regulating the circadian clock and also an inhibitory effect on insulin...
متن کاملThe Soluble Carrier 30 A8 (SLC30A8) Gene Polymorphism and Risk of Diabetes Mellitus Type 2 in Eastern Azerbijan Population of Iran
Type 2 Diabetes Mellitus (T2D) is the most common metabolic disease demonstrating itself by hyper- glycemia, due to impaired insulin secretion or action. Recently, Whole-Genome Association studies have revealed the role of several new genes responsible for T2D. One of the most studied genes is SLC30A8 (Zn-T8) which is exclusively expressed in pancreatic ?-cells and participates in insulin stora...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Diabetes
دوره 57 6 شماره
صفحات -
تاریخ انتشار 2008