title: The codon 17 polymorphism of the CTLA4 gene in type 2 diabetes mellitus.
abstract: 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.
authors.affiliation: Medical Department I, Centre of Internal Medicine, Klinikum of the Johann Wolfgang Goethe-University, 60590 Frankfurt/Main, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Rau
authors.forename: J
authors.initials: J
authors.lastname: Braun
authors.forename: H
authors.initials: H
authors.lastname: Donner
authors.forename: J
authors.initials: J
authors.lastname: Seissler
authors.forename: T
authors.initials: T
authors.lastname: Siegmund
authors.forename: K H
authors.initials: KH
authors.lastname: Usadel
authors.forename: K
authors.initials: K
authors.lastname: Badenhoop
mesh_terms: D000069594:Abatacept; D019943:Amino Acid Substitution; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D002096:C-Peptide / Q000097:blood; D060908:CTLA-4 Antigen; D003062:Codon; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000235:genetics / Q000276:immunology; D003928:Diabetic Nephropathies / Q000235:genetics / Q000276:immunology; D003929:Diabetic Neuropathies / Q000235:genetics / Q000276:immunology; D003930:Diabetic Retinopathy / Q000235:genetics / Q000276:immunology; D005260:Female; D005858:Germany; D006683:HLA-DQ Antigens / Q000235:genetics; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006801:Humans; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D012016:Reference Values; D044465:White People
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D002096:C-Peptide; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D003062:Codon; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments; D000069594:Abatacept