Laboratório de Carboidratos e Radioimunoensaio (LIM 18), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Avenida Dr. Arnaldo 455, 01246-903 São Paulo, SP, Brazil.
Departamento de Genética e Biologia Evolutiva, Instituto de Biociências da Universidade de São Paulo, Rua do Matão 277, 05422-970 São Paulo, SP, Brazil.
Mediators Inflamm. 2014;2014:694948. doi: 10.1155/2014/694948. Epub 2014 May 7.
CD226 rs763361 variant increases susceptibility to type 1 diabetes (T1D) in Caucasians. There is no data about CD226 variants in the very heterogeneous Brazilian population bearing a wide degree of admixture. We investigated its association with T1D susceptibility, clinical phenotypes, and autoimmune manifestations (islet and extrapancreatic autoantibodies). Casuistry. 532 T1D patients and 594 controls in a case-control study. Initially, CD226 coding regions and boundaries were sequenced in a subset of 106 T1D patients and 102 controls. In a second step, two CD226 variants, rs763361 (exon 7) and rs727088 (3' UTR region), involved with CD226 regulation, were genotyped in the entire cohort. C-peptide and autoantibody levels were determined. No new polymorphic variant was found. The variants rs763361 and rs727088 were in strong linkage disequilibrium. The TT genotype of rs763361 was associated with TID risk (OR = 1.503; 95% CI = 1.135-1.991; P = 0.0044), mainly in females (P = 0.0012), greater frequency of anti-GAD autoantibody (31.9% × 24.5%; OR = 1.57; CI = 1.136-2.194; P = 0.0081), and lower C-peptide levels when compared to those with TC + CC genotypes (0.41 ± 0.30 ng/dL versus 0.70 ± 0.53 ng/dL P = 0.0218). Conclusions. The rs763361 variant of CD226 gene (TT genotype) was associated with susceptibility to T1D and with the degree of aggressiveness of the disease in T1D patients from Brazil. Ancestry had no effect.
CD226 rs763361 变异增加了高加索人群患 1 型糖尿病 (T1D) 的易感性。在巴西这个高度混杂的人群中，关于 CD226 变异的数据尚不清楚，这些人群存在广泛程度的混合。我们研究了它与 T1D 易感性、临床表型和自身免疫表现（胰岛和胰外自身抗体）的关联。病例对照研究。532 例 T1D 患者和 594 例对照。最初，在 106 例 T1D 患者和 102 例对照中，我们对 CD226 编码区和边界进行了亚组测序。在第二步中，我们对整个队列进行了 CD226 两个变体 rs763361（外显子 7）和 rs727088（3'UTR 区域）的基因分型，这两个变体与 CD226 调节有关。测定 C 肽和自身抗体水平。未发现新的多态性变异。rs763361 和 rs727088 变体处于强连锁不平衡状态。rs763361 的 TT 基因型与 TID 风险相关（OR = 1.503；95%CI = 1.135-1.991；P = 0.0044），主要在女性中（P = 0.0012），抗 GAD 自身抗体的频率更高（31.9%×24.5%；OR = 1.57；CI = 1.136-2.194；P = 0.0081），与 TC + CC 基因型相比，C 肽水平更低（0.41 ± 0.30ng/dL 与 0.70 ± 0.53ng/dL，P = 0.0218）。结论。CD226 基因 rs763361 变体（TT 基因型）与巴西 T1D 患者的 T1D 易感性和疾病的侵袭性程度相关。遗传背景没有影响。
