The codon 17 polymorphism of the CTLA4 gene in type 2 diabetes mellitus

• Published in: The journal of clinical endocrinology and metabolism 2001-02, Vol.86 (2), p.653-655
• Main Authors: RAU, Harald, BRAUN, Jens, DONNER, Horst, SEISSLER, Jochen, SIEGMUND, Thorsten, USADEL, Klaus H, BADENHOOP, Klaus
• Format: Article
• Language: English
• Subjects: Abatacept; Amino Acid Substitution; Antigens, CD; Antigens, Differentiation - genetics; Biological and medical sciences; C-Peptide - blood; Codon; CTLA-4 Antigen; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - immunology; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Diabetic Angiopathies - genetics; Diabetic Angiopathies - immunology; Diabetic Nephropathies - genetics; Diabetic Nephropathies - immunology; Diabetic Neuropathies - genetics; Diabetic Neuropathies - immunology; Diabetic Retinopathy - genetics; Diabetic Retinopathy - immunology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; European Continental Ancestry Group; Female; Germany; HLA-DQ alpha-Chains; HLA-DQ Antigens - genetics; HLA-DQ beta-Chains; Humans; Immunoconjugates; Immunoglobulin Fc Fragments - genetics; Male; Medical sciences; Middle Aged; Phenotype; Polymorphism, Genetic; Reference Values
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.86.2.653

Several studies have demonstrated an association of CTLA4 (IDDM12) alanine-17 with type 1 diabetes, but CTLA4 variants have not yet been investigated in type 2 diabetes. The CTLA4 exon 1 polymorphism (49 A/G) was analyzed in 300 Caucasian patients with type 2 diabetes and 466 healthy controls. All patients were negative for glutamate decarboxylase and islet cell antibodies. CTLA4 alleles were defined by PCR, single-strand conformational polymorphism, and restriction length fragment polymorphism analysis using BBV:I. The distribution of alleles as well as the genotypic and phenotypic frequencies were similar among patients and controls [AA, 42 vs. 39%; AG, 47 vs. 46%; GG, 11 vs. 15%, P = not significant (n.s.); A/G, 65/35% vs. 62/38%, P = n.s.; alanine/threonine 92/58% vs. 85/61%, P = n.s.]. However, detailed analysis of clinical and biochemical parameters revealed a tendency of GG (alanine/alanine) toward younger age at disease manifestation (46.8 +/- 0.8 vs. 49.5 +/- 0.8 yr, mean +/- SEM), lower body mass index (21.4 +/- 0.5 vs. 24.4 +/- 0.5 kg/m(2), P = 0.042), and basal C-peptide level (0.33 +/- 0.07 vs. 0.53 +/- 0.07nmol/L), as well as earlier start of insulin treatment (5.8 +/- 1.2 vs. 8.7 +/- 0.6 yr) and higher portion of patients on insulin (71 vs. 61%). Patients with the AA genotype were significantly less likely to develop microangiopathic lesions (P < 0.0005). No differences were found for hypertension or family history of type 2 diabetes. In conclusion, CTLA4 alanine-17 does not represent a major risk factor for type 2 diabetes. Additional studies on larger groups and different ethnic groups are warranted to clarify the association of the GG genotype with faster ss-cell failure and the lower rate of microvascular complications in AA carriers.