Association between the transmembrane region polymorphism of MHC class I chain related Gene-A and type 1 diabetes mellitus in Sweden

• Published in: Human immunology Vol. 64; no. 5; pp. 553 - 561
• Main Authors: Gupta, Manu, Nikitina-Zake, Liene, Zarghami, Marjan, Landin-Olsson, Mona, Kockum, Ingrid, Lernmark, Åke, Sanjeevi, Carani B
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2003
• Subjects: Adolescent; Adult; age; Age Factors; Age of Onset; autoimmune disease; Basic Medicine; Case-Control Studies; Child; Child, Preschool; Diabetes Mellitus, Type 1 - epidemiology; Diabetes Mellitus, Type 1 - genetics; Female; gender; Gene Frequency; Genetic Predisposition to Disease; Genotype; Histocompatibility Antigens Class I - genetics; HLA; Humans; Immunologi inom det medicinska området; Immunology in the medical area; Infant; Infant, Newborn; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Polymorphism, Genetic; Sex Factors; Sweden; Swedish population; Sweden; gender; HLA; autoimmune disease; age; Swedish population
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/S0198-8859(03)00035-1

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 ≤ 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 ≤ 20 years old; and negative association of MIC-A6 was stronger in younger onset patients than in older onset patients.