Santiago Jose Luis, Martínez Alfonso, de la Calle Hermenegildo, Fernández-Arquero Miguel, Figueredo M Angeles, de la Concha Emilio G, Urcelay Elena
Immunology Department, Hospital Universitario San Carlos, Madrid, Spain.
BMC Med Genet. 2006 Jun 23;7:54. doi: 10.1186/1471-2350-7-54.
Type 1 diabetes (T1D) is a chronic, autoimmune and multifactorial disease characterized by abnormal metabolism of carbohydrate and fat. Diminished carnitine plasma levels have been previously reported in T1D patients and carnitine increases the sensitivity of the cells to insulin. Polymorphisms in the carnitine transporters, encoded by the SLC22A4 and SLC22A5 genes, have been involved in susceptibility to two other autoimmune diseases, rheumatoid arthritis and Crohn's disease. For these reasons, we investigated for the first time the association with T1D of six single nucleotide polymorphisms (SNPs) mapping to these candidate genes: slc2F2, slc2F11, T306I, L503F, OCTN2-promoter and OCTN2-intron.
A case-control study was performed in the Spanish population with 295 T1D patients and 508 healthy control subjects. Maximum-likelihood haplotype frequencies were estimated by applying the Expectation-Maximization (EM) algorithm implemented by the Arlequin software.
When independently analyzed, one of the tested polymorphisms in the SLC22A4 gene at 1672 showed significant association with T1D in our Spanish cohort. The overall comparison of the inferred haplotypes was significantly different between patients and controls (chi2 = 10.43; p = 0.034) with one of the haplotypes showing a protective effect for T1D (rs3792876/rs1050152/rs2631367/rs274559, CCGA: OR = 0.62 (0.41-0.93); p = 0.02).
The haplotype distribution in the carnitine transporter locus seems to be significantly different between T1D patients and controls; however, additional studies in independent populations would allow to confirm the role of these genes in T1D risk.
1型糖尿病（T1D）是一种慢性、自身免疫性和多因素疾病，其特征为碳水化合物和脂肪代谢异常。先前有报道称T1D患者血浆肉碱水平降低，且肉碱可增加细胞对胰岛素的敏感性。由SLC22A4和SLC22A5基因编码的肉碱转运体的多态性与另外两种自身免疫性疾病——类风湿性关节炎和克罗恩病的易感性有关。基于这些原因，我们首次研究了定位到这些候选基因的六个单核苷酸多态性（SNP）与T1D的关联：slc2F2、slc2F11、T306I、L503F、OCTN2启动子和OCTN2内含子。
在西班牙人群中开展了一项病例对照研究，纳入295例T1D患者和508名健康对照者。通过应用Arlequin软件实施的期望最大化（EM）算法估计最大似然单倍型频率。
单独分析时，SLC22A4基因中位于1672处的一个检测多态性在我们的西班牙队列中显示出与T1D存在显著关联。推断单倍型在患者和对照之间的总体比较存在显著差异（卡方=10.43；p = 0.034），其中一种单倍型对T1D具有保护作用（rs3792876/rs1050152/rs2631367/rs274559，CCGA：比值比=0.62（0.41 - 0.93）；p = 0.02）。
肉碱转运体基因座中的单倍型分布在T1D患者和对照之间似乎存在显著差异；然而，在独立人群中开展的进一步研究将有助于确认这些基因在T1D风险中的作用。
