Unidad de Endocrinología Pediátrica, Complejo Hospitalario Universitario Insular Materno Infantil de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
Asociación Canaria para la Investigación Pediátrica (ACIP canarias), Las Palmas, Spain.
BMC Pediatr. 2024 Sep 6;24(1):569. doi: 10.1186/s12887-024-04983-w.
The Canary Islands inhabitants, a recently admixed population with significant North African genetic influence, has the highest incidence of childhood-onset type 1 diabetes (T1D) in Spain and one of the highest in Europe. HLA accounts for half of the genetic risk of T1D.
To characterize the classical HLA-DRB1 and HLA-DQB1 alleles in children from Gran Canaria with and without T1D.
We analyzed classic HLA-DRB1 and HLA-DQB1 alleles in childhood-onset T1D patients (n = 309) and control children without T1D (n = 222) from the island of Gran Canaria. We also analyzed the presence or absence of aspartic acid at position 57 in the HLA-DQB1 gene and arginine at position 52 in the HLA-DQA1 gene. Genotyping of classical HLA-DQB1 and HLA-DRB1 alleles was performed at two-digit resolution using Luminex technology. The chi-square test (or Fisher's exact test) and odds ratio (OR) were computed to assess differences in allele and genotype frequencies between patients and controls. Logistic regression analysis was also used.
Mean age at diagnosis of T1D was 7.4 ± 3.6 years (46% female). Mean age of the controls was 7.6 ± 1.1 years (55% female). DRB103 (OR = 4.2; p = 2.13), DRB104 (OR = 6.6; p ≤ 2.00), DRB1* 07 (OR = 0.37; p = 9.73), DRB111 (OR = 0.17; p = 6.72), DRB112, DRB113 (OR = 0.38; p = 1.21), DRB114 (OR = 0.0; p = 0.0024), DRB115 (OR = 0.13; p = 7.78) and DRB116 (OR = 0.21; p = 0.003) exhibited significant differences in frequency between groups. Among the DQB1* alleles, DQB102 (OR: 2.3; p = 5.13), DQB103 (OR = 1.7; p = 1.89), DQB105 (OR = 0.64; p = 0.027) and DQB106 (OR = 0.19; p = 6.25) exhibited significant differences. A total of 58% of the studied HLA-DQB1 genes in our control population lacked aspartic acid at position 57.
In this population, the overall distributions of the HLA-DRB1 and HLA-DQB1 alleles are similar to those in other European populations. However, the frequency of the non-Asp-57 HLA-DQB1 molecules is greater than that in other populations with a lower incidence of T1D. Based on genetic, historical and epidemiological data, we propose that a common genetic background might help explain the elevated pediatric T1D incidence in the Canary Islands, North-Africa and middle eastern countries.
分析加那利群岛儿童 1 型糖尿病（T1D）患者和非 T1D 对照儿童 HLA-DRB1 和 HLA-DQB1 等位基因的特征。
我们分析了来自大加那利岛的儿童 T1D 患者（n=309）和无 T1D 的对照儿童（n=222）的经典 HLA-DRB1 和 HLA-DQB1 等位基因。我们还分析了 HLA-DQB1 基因第 57 位天冬氨酸和 HLA-DQA1 基因第 52 位精氨酸的存在或缺失。使用 Luminex 技术以两位数字分辨率进行经典 HLA-DQB1 和 HLA-DRB1 等位基因的基因分型。采用卡方检验（或 Fisher 确切概率法）和比值比（OR）评估患者和对照组之间等位基因和基因型频率的差异。还进行了 logistic 回归分析。
T1D 的平均诊断年龄为 7.4±3.6 岁（46%为女性）。对照组的平均年龄为 7.6±1.1 岁（55%为女性）。DRB103（OR=4.2；p=2.13）、DRB104（OR=6.6；p≤2.00）、DRB107（OR=0.37；p=9.73）、DRB111（OR=0.17；p=6.72）、DRB112、DRB113（OR=0.38；p=1.21）、DRB114（OR=0.0；p=0.0024）、DRB115（OR=0.13；p=7.78）和 DRB116（OR=0.21；p=0.003）在组间频率上有显著差异。在 DQB1等位基因中，DQB102（OR：2.3；p=5.13）、DQB103（OR=1.7；p=1.89）、DQB105（OR=0.64；p=0.027）和 DQB106（OR=0.19；p=6.25）有显著差异。我们对照组中 58%的 HLA-DQB1 基因缺乏第 57 位天冬氨酸。
在该人群中，HLA-DRB1 和 HLA-DQB1 等位基因的总体分布与其他欧洲人群相似。然而，非 Asp-57 HLA-DQB1 分子的频率高于其他 T1D 发病率较低的人群。基于遗传、历史和流行病学数据，我们提出共同的遗传背景可能有助于解释加那利群岛、北非和中东国家儿童 1 型糖尿病发病率升高的现象。
