Yeray Nóvoa-Medina, Itahisa Marcelino-Rodriguez, Nicolás M Suárez, Marta Barreiro-Bautista, Eva Rivas-García, Santiago Sánchez-Alonso, Gema González-Martínez, Sofía Quinteiro-González, Ángela Domínguez, María Cabrera, Sara López, Svetlana Pavlovic, Carlos Flores, Ana M Wägner
{"title":"HLA 是否能解释加那利群岛儿童期 1 型糖尿病的高发病率？Asp57 DQB1 分子的作用。","authors":"Yeray Nóvoa-Medina, Itahisa Marcelino-Rodriguez, Nicolás M Suárez, Marta Barreiro-Bautista, Eva Rivas-García, Santiago Sánchez-Alonso, Gema González-Martínez, Sofía Quinteiro-González, Ángela Domínguez, María Cabrera, Sara López, Svetlana Pavlovic, Carlos Flores, Ana M Wägner","doi":"10.1186/s12887-024-04983-w","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p><p><strong>Aims: </strong>To characterize the classical HLA-DRB1 and HLA-DQB1 alleles in children from Gran Canaria with and without T1D.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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). DRB1*03 (OR = 4.2; p = 2.13<sup>-13</sup>), DRB1*04 (OR = 6.6; p ≤ 2.00<sup>-16</sup>), DRB1* 07 (OR = 0.37; p = 9.73<sup>-06</sup>), DRB1*11 (OR = 0.17; p = 6.72<sup>-09</sup>), DRB1*12, DRB1*13 (OR = 0.38; p = 1.21<sup>-05</sup>), DRB1*14 (OR = 0.0; p = 0.0024), DRB1*15 (OR = 0.13; p = 7.78<sup>-07</sup>) and DRB1*16 (OR = 0.21; p = 0.003) exhibited significant differences in frequency between groups. Among the DQB1* alleles, DQB1*02 (OR: 2.3; p = 5.13<sup>-06</sup>), DQB1*03 (OR = 1.7; p = 1.89<sup>-03</sup>), DQB1*05 (OR = 0.64; p = 0.027) and DQB1*06 (OR = 0.19; p = 6.25<sup>-14</sup>) exhibited significant differences. A total of 58% of the studied HLA-DQB1 genes in our control population lacked aspartic acid at position 57.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":9144,"journal":{"name":"BMC Pediatrics","volume":null,"pages":null},"PeriodicalIF":2.0000,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378579/pdf/","citationCount":"0","resultStr":"{\"title\":\"Does HLA explain the high incidence of childhood-onset type 1 diabetes in the Canary Islands? The role of Asp57 DQB1 molecules.\",\"authors\":\"Yeray Nóvoa-Medina, Itahisa Marcelino-Rodriguez, Nicolás M Suárez, Marta Barreiro-Bautista, Eva Rivas-García, Santiago Sánchez-Alonso, Gema González-Martínez, Sofía Quinteiro-González, Ángela Domínguez, María Cabrera, Sara López, Svetlana Pavlovic, Carlos Flores, Ana M Wägner\",\"doi\":\"10.1186/s12887-024-04983-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p><p><strong>Aims: </strong>To characterize the classical HLA-DRB1 and HLA-DQB1 alleles in children from Gran Canaria with and without T1D.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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). DRB1*03 (OR = 4.2; p = 2.13<sup>-13</sup>), DRB1*04 (OR = 6.6; p ≤ 2.00<sup>-16</sup>), DRB1* 07 (OR = 0.37; p = 9.73<sup>-06</sup>), DRB1*11 (OR = 0.17; p = 6.72<sup>-09</sup>), DRB1*12, DRB1*13 (OR = 0.38; p = 1.21<sup>-05</sup>), DRB1*14 (OR = 0.0; p = 0.0024), DRB1*15 (OR = 0.13; p = 7.78<sup>-07</sup>) and DRB1*16 (OR = 0.21; p = 0.003) exhibited significant differences in frequency between groups. Among the DQB1* alleles, DQB1*02 (OR: 2.3; p = 5.13<sup>-06</sup>), DQB1*03 (OR = 1.7; p = 1.89<sup>-03</sup>), DQB1*05 (OR = 0.64; p = 0.027) and DQB1*06 (OR = 0.19; p = 6.25<sup>-14</sup>) exhibited significant differences. A total of 58% of the studied HLA-DQB1 genes in our control population lacked aspartic acid at position 57.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":9144,\"journal\":{\"name\":\"BMC Pediatrics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-09-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378579/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Pediatrics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12887-024-04983-w\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PEDIATRICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Pediatrics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12887-024-04983-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PEDIATRICS","Score":null,"Total":0}
Does HLA explain the high incidence of childhood-onset type 1 diabetes in the Canary Islands? The role of Asp57 DQB1 molecules.
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.
Aims: To characterize the classical HLA-DRB1 and HLA-DQB1 alleles in children from Gran Canaria with and without T1D.
Methods: 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.
Results: 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). DRB1*03 (OR = 4.2; p = 2.13-13), DRB1*04 (OR = 6.6; p ≤ 2.00-16), DRB1* 07 (OR = 0.37; p = 9.73-06), DRB1*11 (OR = 0.17; p = 6.72-09), DRB1*12, DRB1*13 (OR = 0.38; p = 1.21-05), DRB1*14 (OR = 0.0; p = 0.0024), DRB1*15 (OR = 0.13; p = 7.78-07) and DRB1*16 (OR = 0.21; p = 0.003) exhibited significant differences in frequency between groups. Among the DQB1* alleles, DQB1*02 (OR: 2.3; p = 5.13-06), DQB1*03 (OR = 1.7; p = 1.89-03), DQB1*05 (OR = 0.64; p = 0.027) and DQB1*06 (OR = 0.19; p = 6.25-14) exhibited significant differences. A total of 58% of the studied HLA-DQB1 genes in our control population lacked aspartic acid at position 57.
Conclusions: 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.
期刊介绍：
BMC Pediatrics is an open access journal publishing peer-reviewed research articles in all aspects of health care in neonates, children and adolescents, as well as related molecular genetics, pathophysiology, and epidemiology.
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