title: Association between the transmembrane region polymorphism of MHC class I chain related gene-A and type 1 diabetes mellitus in Sweden.
abstract: Major histocompatibility complex (MHC) class I chain related gene-A (MIC-A) is associated with type 1 diabetes mellitus (T1DM) in other populations. We tested the association of MIC-A gene polymorphism with T1DM in Swedish Caucasians; if it has an age-dependent association; and if the association has an effect on gender. We studied 635 T1DM patients and 503 matched controls in the age group of 0-35 years old. MIC-A5 was significantly increased in T1DM compared with controls (odds ratio [OR] =1.81, p(c) < 0.0005). Logistic regression analysis revealed MIC-A5 association was independent of HLA. MIC-A5 with DR4-DQ8 or MIC-A5 with DR3-DQ2 gave higher OR than the OR obtained with either of them alone (OR = 1.81, 7.1, and 3.6, respectively). MIC-A5 was positively (OR = 2.48, p(c) < 0.0005) and MIC-A6 negatively associated (OR = 0.61, p(c) = 0.035) with the disease in < or = 20 years of age. The negative association of MIC-A6 in young onset was confirmed by logistic regression analysis. MIC-A5 was associated with the disease in males (OR = 2.05, p(c) = 0.0005). MIC-A6 conferred protection (OR = 0.098, p(c) = 0.032) in females heterozygous for DR3/DR4. In conclusion, MIC-A5 is associated with T1DM; the association was higher in individuals < or = 20 years old; and negative association of MIC-A6 was stronger in younger onset patients than in older onset patients.
authors.affiliation: Department of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Manu
authors.initials: M
authors.lastname: Gupta
authors.forename: Liene
authors.initials: L
authors.lastname: Nikitina-Zake
authors.forename: Marjan
authors.initials: M
authors.lastname: Zarghami
authors.forename: Mona
authors.initials: M
authors.lastname: Landin-Olsson
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kockum
authors.forename: Ake
authors.initials: A
authors.lastname: Lernmark
authors.forename: Carani B
authors.initials: CB
authors.lastname: Sanjeevi
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011110:Polymorphism, Genetic; D012737:Sex Factors; D013548:Sweden
chemical_list: D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A