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

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 I polymorphism (49 A/G) was analyzed in 300 Caucasian patients with type 2 diabetes and 466 healthy controls. All p atients were negative for glutamate decarboxylase and islet cell antibodies . CTLA4 alleles were defined by PCR, single-strand conformational polymorph ism, and restriction length fragment polymorphism analysis using BbvI. 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% us. 62/38%, P = n.s .; alanine/threonine 92/58% vs. 85/61%, P = n.s.]. However, detailed analys is of clinical and biochemical parameters revealed a tendency of GG (alanin e/alanine) toward younger age at disease manifestation(46.8 +/- 0.8 us. 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. 0.5 3 +/- 0.07 nmol/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. 6 1%). Patients with the AA genotype were significantly less likely to develo p microangiopathic lesions (P < 0.0005). No differences were found for hype rtension 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 clari fy the association of the GG genotype with faster p-cell failure and the lo wer rate of microvascular complications in AA carriers.