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Diaz-Valencia PA, Bougnères P, Valleron AJ. Covariation of the incidence of type 1 diabetes with country characteristics available in public databases. PLoS One 2015; 10:e0118298. [PMID: 25706995 PMCID: PMC4338253 DOI: 10.1371/journal.pone.0118298] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2014] [Accepted: 12/24/2014] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The incidence of Type 1 Diabetes (T1D) in children varies dramatically between countries. Part of the explanation must be sought in environmental factors. Increasingly, public databases provide information on country-to-country environmental differences. METHODS Information on the incidence of T1D and country characteristics were searched for in the 194 World Health Organization (WHO) member countries. T1D incidence was extracted from a systematic literature review of all papers published between 1975 and 2014, including the 2013 update from the International Diabetes Federation. The information on country characteristics was searched in public databases. We considered all indicators with a plausible relation with T1D and those previously reported as correlated with T1D, and for which there was less than 5% missing values. This yielded 77 indicators. Four domains were explored: Climate and environment, Demography, Economy, and Health Conditions. Bonferroni correction to correct false discovery rate (FDR) was used in bivariate analyses. Stepwise multiple regressions, served to identify independent predictors of the geographical variation of T1D. FINDINGS T1D incidence was estimated for 80 WHO countries. Forty-one significant correlations between T1D and the selected indicators were found. Stepwise Multiple Linear Regressions performed in the four explored domains indicated that the percentages of variance explained by the indicators were respectively 35% for Climate and environment, 33% for Demography, 45% for Economy, and 46% for Health conditions, and 51% in the Final model, where all variables selected by domain were considered. Significant environmental predictors of the country-to-country variation of T1D incidence included UV radiation, number of mobile cellular subscriptions in the country, health expenditure per capita, hepatitis B immunization and mean body mass index (BMI). CONCLUSIONS The increasing availability of public databases providing information in all global environmental domains should allow new analyses to identify further geographical, behavioral, social and economic factors, or indicators that point to latent causal factors of T1D.
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Affiliation(s)
- Paula Andrea Diaz-Valencia
- Institut National de la Santé et de la Recherche Médicale, Inserm Unité-1169, F-94276, Le Kremlin Bicêtre, France
- Université Pierre et Marie Curie-Paris 6, Ecole Doctorale 393, F-75012, Paris, France
| | - Pierre Bougnères
- Institut National de la Santé et de la Recherche Médicale, Inserm Unité-1169, F-94276, Le Kremlin Bicêtre, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Kremlin Bicêtre, Service Endocrinologie, F-94276, Le Kremlin Bicêtre, France
| | - Alain-Jacques Valleron
- Institut National de la Santé et de la Recherche Médicale, Inserm Unité-1169, F-94276, Le Kremlin Bicêtre, France
- Université Pierre et Marie Curie-Paris 6, Ecole Doctorale 393, F-75012, Paris, France
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Mosaad YM, Auf FA, Metwally SS, Elsharkawy AA, El-Hawary AK, Hassan RH, Tawhid ZE, El-Chennawi FA. HLA-DQB1* alleles and genetic susceptibility to type 1 diabetes mellitus. World J Diabetes 2012; 3:149-55. [PMID: 22919445 PMCID: PMC3425629 DOI: 10.4239/wjd.v3.i8.149] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2012] [Revised: 06/27/2012] [Accepted: 08/08/2012] [Indexed: 02/05/2023] Open
Abstract
AIM: To determine human leukocyte antigen (HLA)-DQB1 allele association with susceptibility to type 1 diabetes (T1D) and to clinical and laboratory findings.
METHODS: This study was conducted on 85 unrelated Egyptian children with T1D recruited consecutively from the Pediatric Diabetes Endocrinology outpatients Clinic; Mansoura University Children’s Hospital, Egypt. Patient mean follow up period was 2.5 years. Patients were subdivided according to level of HbA1c (optimal/suboptimal control < 8.5% and poor control ≥ 8.5%). The control group consisted of 113 unrelated age- and sex-matched healthy subjects without T1D or other autoimmune diseases. Genomic DNA extraction was done for all subjects using a DNA isolation kit. HLA-Class II-DQB1 allele typing was carried out with a polymerase chain reaction-sequence-specific oligonucleotide probe using a INNO-LiPA HLA-DQB1 update kit.
RESULTS: Significant differences were detected between Egyptian patients with T1D and control groups in the frequencies of DQB1*02 [44.4% vs 18.6%, corrected P value (Pc) < 0.001] and DQB1*03 (41.2% vs 24.4%, Pc < 0.001). Significant differences were also observed between control groups and T1D patients in the frequencies of DQB1*05 (14.6% vs 7.2%, P = 0.029) and DQB1*06 (34.1% vs 7.2%, P < 0.001). However, after correction for multiple comparisons, the significance was retained for HLA-DQB1*06 (Pc < 0.001) but lost for HLA-DQB1*05. HLA-DQB1*0201, *0202, *030201 were positively associated with T1D (Pc = 0.014, Pc < 0.001, and Pc < 0.001 respectively), while HLA-DQB1*060101 was negatively associated (Pc < 0.001) with the condition. Although the HLA-DQB1 alleles 030101 and 050101 were significantly higher in controls (P = 0.016, P = 0.025 respectively), both of them lost statistical significance after correction of P value. The frequency of the HLA-DQB1 genotypes 02/02, 02/03, and 03/03 was higher in T1D patients, and the frequency of the genotypes 03/06, 05/06, and 06/06 was higher in controls, these differences being statistically significant before correction. After correction, the genotypes 02/02, 02/03 in T1D, and the genotypes 03/06, 06/06 in controls were still significant (Pc = 0.01, Pc < 0.001, Pc < 0.001, and Pc = 0.04, respectively). Non-significant associations were found between the frequency HLA-DQB1 alleles and genotypes in T1D in relation to the grade of diabetic control, Microalbuminuria, age, gender, age of presentation, weight, height, frequency of diabetic ketoacidosis (P = 0.42), serum cholesterol, and fasting and post-prandial level of C-peptide (P = 0.83, P = 0.9, respectively).
CONCLUSION: The Current work suggests that HLA-DQB1 alleles *030201, *0202, *0201, and genotypes 02/03, 02/02 may be susceptibility risk factors for development of T1D in Egyptian children, while the HLA-DQB1*060101 allele, and 03/06, 06/06 genotypes may be protective factors. HLA-DQB1 alleles and genotypes do not contribute to microalbuminuria or grade of diabetic control.
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Affiliation(s)
- Youssef M Mosaad
- Youssef M Mosaad, Fatma A Auf, Shereen S Metwally, Ziyad E Tawhid, Farha A El-Chennawi, Unit of Clinical Immunology, Department of Clinical Pathology, Mansoura Faculty of Medicine, Mansoura 35111, Egypt
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Rojas-Villarraga A, Botello-Corzo D, Anaya JM. HLA-Class II in Latin American patients with type 1 diabetes. Autoimmun Rev 2010; 9:666-73. [DOI: 10.1016/j.autrev.2010.05.016] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2010] [Accepted: 05/17/2010] [Indexed: 12/28/2022]
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Pérez-Bravo F, Martinez-Laso J, Martin-Villa JM, Moscoso J, Moreno A, Serrano-Vela JI, Zamora J, Asenjo S, Gleisner A, Arnaiz-Villena A. HLA non-class II genes may confer type I diabetes susceptibility in a Mapuche (Amerindian) affected family. Eur J Med Genet 2006; 49:37-41. [PMID: 16473308 DOI: 10.1016/j.ejmg.2005.01.027] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
A rare case of type I diabetes is studied in an Amerindian (Mapuche) family from Chile, analyzing glutamic acid decarboxylase, islet-cell autoantibodies and human leukocyte antigen (HLA) genes. The affected sib is the only one that has one specific HLA haplotype combination that differs from the other sibs only in the HLA class I genes. It is concluded that HLA diabetes susceptibility factors may be placed outside the class II region or even that susceptibility factors do not exist in the HLA region in this Amerindian family.
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Moussa MAA, Alsaeid M, Abdella N, Refai TMK, Al-Sheikh N, Gomez JE. Prevalence of type 1 diabetes among 6- to 18-year-old Kuwaiti children. Med Princ Pract 2005; 14:87-91. [PMID: 15785099 DOI: 10.1159/000083917] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2003] [Accepted: 03/22/2004] [Indexed: 02/02/2023] Open
Abstract
OBJECTIVES To determine the prevalence of type 1 diabetes among 6- to 18-year-old Kuwaiti children according to gender, age, and region. SUBJECTS AND METHODS Children with type 1 diabetes aged 6-18 years were identified at 182 schools (50 primary, 63 intermediate, and 69 secondary) in Kuwait during the study period October 2000 to September 2002. Schools were randomly selected using the 2000/01 educational districts' registers as sampling frame proportional to the number of schools in each district. Prevalence rates were adjusted to the 2002 Kuwaiti population. Diagnosis of type 1 diabetes was based on the World Health Organization, and the American Diabetes Association criteria. RESULTS Prevalence of type 1 diabetes was 269.9 per 100,000 (95% confidence interval, CI 241.6-298.3). There was no significant difference in prevalence between male (247.6, 95% CI 205.2-290.0) and female (285.5, 95% CI 247.5-323.5). Type 1 diabetes was more prevalent in the age group 10-13 years (347.3), and lowest in the age group 6-9 years (182.6) per 100,000; the difference was significant at p < 0.001. The overall age-adjusted prevalence rate was 252.9 (95% CI 234.6-271.2), 229.1 (95% CI 204.6-253.6) in male and 277.4 (95% CI 250.0-304.7) in female children in the 2002 Kuwaiti population. The mean age at onset was 9.2, and 8.1 years in male and female children, respectively (p = 0.018). There was no significant difference in prevalence between regions. CONCLUSION Type 1 diabetes is a common chronic disease in Kuwaiti children.
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Affiliation(s)
- Mohamed A A Moussa
- Department of Community Medicine and Behavioural Sciences, Faculty of Medicine, Kuwait University, Kuwait.
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Kaila B, Taback SP. The effect of day care exposure on the risk of developing type 1 diabetes: a meta-analysis of case-control studies. Diabetes Care 2001; 24:1353-8. [PMID: 11473069 DOI: 10.2337/diacare.24.8.1353] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Exposure to infections in infancy or childhood may be important in the pathogenesis of type 1 diabetes, but a protective role has also been suggested. We tested the hypothesis that increased early contact with infectious agents, measured by day care exposure, would decrease the risk of type 1 diabetes in childhood. RESEARCH DESIGN AND METHODS We conducted a systematic review of case-control studies. Meta-analysis was performed to combine results, assess for heterogeneity, and explore variation in study design. RESULTS Several generally well-designed case-control studies show a statistically significant protective effect of day care on type 1 diabetes. However, meta-analysis revealed too much heterogeneity to accept the overall synthesis results and none of the studies used prerecorded data. Day care does seem to have a protective effect in the subgroup of children who will be diagnosed with type 1 diabetes before the age of 5 years (odds ratio = 0.6, 95% CI 0.5-0.8); however, this result is based on only two studies. CONCLUSIONS Recall bias is one alternate explanation for these data; confirmation using prerecorded data is required. Such data could be prospectively measured in cohort studies of children at risk. We also suggest that information about day care attendance be measured in randomized trials of agents for the prevention of type 1 diabetes, as day care exposure could potentially modify the effect of the preventive agent.
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Affiliation(s)
- B Kaila
- Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada
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Pirie FJ, Hammond MG, Motala AA, Omar MA. HLA class II antigens in South African Blacks with type I diabetes. TISSUE ANTIGENS 2001; 57:348-52. [PMID: 11380945 DOI: 10.1034/j.1399-0039.2001.057004348.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Type 1 diabetes mellitus is poorly characterised in many African communities, including South Africa, where little is known of the disease epidemiology. This study aimed to identify the HLA class II alleles associated with type 1 diabetes in a group of Zulu subjects in Durban, KwaZulu-Natal by PCR-SSP. The HLA alleles associated with type 1 diabetes included HLA-DQB*0302 (P<0.0001), DRB1*O9 (P<0.0001), DRB1*04 (P=0.002), DRB1*0301 (P=0.003), DQB*02 (P=0.004) and DQA*03 (P=0.035). Estimated haplotypes positively associated with type 1 diabetes included HLA-DRB1 *0301-DQA*0501, DRB1*04-DQA*03, DRB1*04-DQB*0302, DRB1*0301-DQB*0201, DQA*0501-DQB*0201 and DQA*03-DQB*0302. These findings are similar to those reported from Zimbabwe and other populations with type 1 diabetes.
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Affiliation(s)
- F J Pirie
- Department of Medicine, University of Natal, Congella, South Africa.
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Abstract
UNLABELLED The aims of this study were to estimate the prevalence of coeliac disease (CD) in Czech children with insulin dependent diabetes mellitus (IDDM), and to determine the contribution of HLA-DQA1 and DQB1 to CD susceptibility among diabetic children. We screened 345 children with IDDM (186 boys and 159 girls, aged 0 to 18 y) for coeliac disease using the IgA endomysial antibodies (EMA) test. In all EMA-positive children, small bowel biopsy was performed to confirm CD. To determine the role of the HLA-DQA1*05-DQB1*0201 (DQ2) and the DQA1*03-DQB1*0302 (DQ8) molecules in CD susceptibility among diabetic children, the HLA-DQA1-DQB1 was genotyped in all EMA-positive, and in 186 of EMA-negative diabetic patients. EMA positivity was found in 15/345 (4.3%) diabetic children. The diagnosis of CD was established in 14/345 (4.1%) children based on a bioptic finding of villous atrophy, while the remaining EMA-positive patient had a normal bioptic finding, being diagnosed as a potential CD. The HLA DQA1*05-DQB1*0201 (DQ2) molecule conferred a significant risk of CD among diabetic children (odds ratio = 4.1, CI 95% 1.1-15), being found more frequently in diabetic children with CD (80%) than in diabetic children without CD (49%). CONCLUSION The high prevalence of CD (4.1%) found in Czech children with IDDM emphasizes the need for their regular screening. We suggest that this CD screening protocol may be individualized according to the DQA1*05-DQB1*0201 positivity.
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Roy MA, Mérette C, Maziade M. [Introduction to genetic psychiatry: progress in uncovering genetic susceptibility to psychiatric disorders]. CANADIAN JOURNAL OF PSYCHIATRY. REVUE CANADIENNE DE PSYCHIATRIE 2001; 46:52-60. [PMID: 11221490 DOI: 10.1177/070674370104600108] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
The recent progress in human genetics suggests major benefits in clinical practice, including psychiatry. This article introduces the research methodology used in psychiatric genetics and explains how it is applied, for a better understanding of the challenges facing psychiatric genetics and the strategies being used to overcome them. We will review the evidence of genetic factors in psychiatric disorder etiology as well as the specificity or non-specificity of their expression. We will discuss problems associated with the approximate nature of diagnostic methods, the incomplete penetrance and the genetic heterogeneity of psychiatric disorders, the presence of phenocopies and our uncertainty concerning the mode of inheritance of psychiatric disorders. Finally, we will provide an overview of the most promising results and set out priorities for future studies.
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Affiliation(s)
- M A Roy
- Département de psychiatrie de la Faculté de médecine de l'Université Laval et centre de recherche Université Laval Robert-Giffard
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Cinek O, Wilkinson E, Paltiel L, Saugstad OD, Magnus P, Rønningen KS. Screening for the IDDM high-risk genotype. A rapid microtitre plate method using serum as source of DNA. TISSUE ANTIGENS 2000; 56:344-9. [PMID: 11098934 DOI: 10.1034/j.1399-0039.2000.560406.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Norwegian babies born with the HLA-DRB1*0401-DQA1*03-DQB1*0302/DRB1*03-DQA1+ ++*05-DQB1*0201 genotype have an estimated 17% lifetime risk of developing insulin-dependent diabetes mellitus (IDDM). Identifying these children is important for future prevention, and for studies of the non-genetic factors involved in IDDM. The aim of the study was to develop a rapid screening method for this high-risk genotype. DNA was extracted from serum collected during routine newborn screening for phenylketonuria and hypothyreosis. The second exons of HLA-DQA1 and DQB1 were co-amplified using biotinylated primers, amplicons were hybridized to a set of seven probes immobilized on a microtitre plate using a single hybridisation temperature, and detected colorimetrically by streptavidin-HRP conjugate and tetramethylbenzidine substrate. The DRB1*04 subtyping was performed using six different probes at identical conditions. The prevalence of the DRB1*0401-DQA1*03-DQB1*0302/DRB1*03-DQA1*0 5-DQB1*0201 genotype among 1,026 Norwegian babies was 2.7% (CI 95%: 1.7-3.7%). The new high-throughput genetic screening method for IDDM risk can easily be automated and included in newborn screening programs.
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Affiliation(s)
- O Cinek
- National Institute of Public Health, Section of Epidmiology, Oslo, Norway
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Santos JL, Pérez-Bravo F, Carrasco E, Petri R, Calvillán M, Albala C. Associations between HLA-DQB1 high-risk alleles and type I diabetes do not depend on cytomegalovirus antibody status at onset: a case-parent study conducted in Chile. Immunol Cell Biol 2000; 78:259-63. [PMID: 10849114 DOI: 10.1046/j.1440-1711.2000.00911.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
The purpose of the present study is to ascertain whether the associations between HLA-DQB1*0201 and DQB1*0302 alleles and childhood diabetes depend on the presence of antibodies to human cytomegalovirus (CMV). A study of incident type I diabetes cases and parents was conducted in Santiago, Chile. HLA-DQB1 polymorphisms were determined in 85 case-parent trios (255 subjects), while the detection of CMV was carried out only in the incident cases. As expected, HLA-DQB1 polymorphisms are strongly associated with type I diabetes, with crude odds ratios of 3.7 (95% confidence interval (CI) 1.8-7.7) for the DQB1*0201 allele and 10.3 (95% CI 5.0-21.4) for the DQB1*0302 allele. In the subset of families with CMV+ cases, the odds ratios were estimated as 3.7 (95% CI 1.6-8.6) for the DQB1*0201 allele and 11.1 (95% CI 4.8-25.8) for the DQB1*0302 allele. In families with patients who tested negative for CMV antibodies, the odds ratios were calculated as 3.5 (95% CI 0.7-16.8) for the DQB1*0201 allele, and 8.0 (95% CI 1.8-34.7) for the DQB1*0302 allele. There was no evidence of statistical interaction between CMV antibodies and the DQB1*0201 allele (P value = 0.9) or the DQB1*0302 allele (P value = 0.7). In conclusion, alleles DQB1*0302 and DQB1*0201 do not display distinct associations with type I diabetes depending on the presence of antibodies for CMV.
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Affiliation(s)
- J L Santos
- Laboratory of Epidemiology, Institute of Nutrition and Food Technology and Division of Diabetes, Hospital San Juan de Dios, Faculty of Medicine, University of Chile, Santiago, Chile
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