Type 1 diabetes in Africa: an immunogenetic study in the Amhara of North-West Ethiopia
Aims/hypothesis We aimed to characterise the immunogenic background of insulin-dependent diabetes in a resource-poor rural African community. The study was initiated because reports of low autoantibody prevalence and phenotypic differences from European-origin cases with type 1 diabetes have raised...
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| Veröffentlicht in: | Diabetologia 2020-10, Vol.63 (10), p.2158-2168 |
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| creator | Balcha, Shitaye A. Demisse, Abayneh G. Mishra, Rajashree Vartak, Tanwi Cousminer, Diana L. Hodge, Kenyaita M. Voight, Benjamin F. Lorenz, Kim Schwartz, Stanley Jerram, Samuel T. Gamper, Arla Holmes, Alice Wilson, Hannah F. Williams, Alistair J. K. Grant, Struan F. A. Leslie, R. David Phillips, David I. W. Trimble, Elisabeth R. |
| description | Aims/hypothesis
We aimed to characterise the immunogenic background of insulin-dependent diabetes in a resource-poor rural African community. The study was initiated because reports of low autoantibody prevalence and phenotypic differences from European-origin cases with type 1 diabetes have raised doubts as to the role of autoimmunity in this and similar populations.
Methods
A study of consecutive, unselected cases of recently diagnosed, insulin-dependent diabetes (
n
= 236, ≤35 years) and control participants (
n
= 200) was carried out in the ethnic Amhara of rural North-West Ethiopia. We assessed their demographic and socioeconomic characteristics, and measured non-fasting C-peptide, diabetes-associated autoantibodies and
HLA-DRB1
alleles. Leveraging genome-wide genotyping, we performed both a principal component analysis and, given the relatively modest sample size, a provisional genome-wide association study. Type 1 diabetes genetic risk scores were calculated to compare their genetic background with known European type 1 diabetes determinants.
Results
Patients presented with stunted growth and low BMI, and were insulin sensitive; only 15.3% had diabetes onset at ≤15 years. C-peptide levels were low but not absent. With clinical diabetes onset at ≤15, 16–25 and 26–35 years, 86.1%, 59.7% and 50.0% were autoantibody positive, respectively. Most had autoantibodies to GAD (GADA) as a single antibody; the prevalence of positivity for autoantibodies to IA-2 (IA-2A) and ZnT8 (ZnT8A) was low in all age groups. Principal component analysis showed that the Amhara genomes were distinct from modern European and other African genomes.
HLA-DRB1*03:01
(
p
= 0.0014) and
HLA-DRB1*04
(
p
= 0.0001) were positively associated with this form of diabetes, while
HLA-DRB1*15
was protective (
p
|
| doi_str_mv | 10.1007/s00125-020-05229-x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7476916</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2440540589</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-7011bf669226a9091099a29d34863793750fa6288023dba60c0d55e4621f428b3</originalsourceid><addsrcrecordid>eNp9kUuLFDEUhYMoTjv6B1xIwM1sojePSiouhGYYHzDoZnzsQqoq1ZWhK2mTlEz_e9P2OD4WQuAuzndP7uEg9JTCCwqgXmYAyhoCDAg0jGlycw-tqOCMgGDtfbQ66IS28usJepTzNQDwRsiH6IQzBQ2ncoU-X-13DlM8eNu54jL2Aa_H5Hv7CtuA_TwvIW5ccMX3OJdl2B-IMjm8niebLI4j_hBTmcgXlwu-KJOPO28fowej3Wb35Haeok9vLq7O35HLj2_fn68vSS-UKEQBpd0opWZMWg2agtaW6YGLVnKluWpgtJK1LTA-dFZCD0PTOCEZHWvEjp-i10ff3dLNbuhdKMluzS752aa9idabv5XgJ7OJ340SSmoqq8HZrUGK35Yawcw-9267tcHFJRsmmOJQDxEVff4Peh2XFGq8Sglo6mt1pdiR6lPMObnx7hgK5lCbOdZmam3mZ23mpi49-zPG3cqvnirAj0CuUti49Pvv_9j-ANAToVI</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2440540589</pqid></control><display><type>article</type><title>Type 1 diabetes in Africa: an immunogenetic study in the Amhara of North-West Ethiopia</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Balcha, Shitaye A. ; Demisse, Abayneh G. ; Mishra, Rajashree ; Vartak, Tanwi ; Cousminer, Diana L. ; Hodge, Kenyaita M. ; Voight, Benjamin F. ; Lorenz, Kim ; Schwartz, Stanley ; Jerram, Samuel T. ; Gamper, Arla ; Holmes, Alice ; Wilson, Hannah F. ; Williams, Alistair J. K. ; Grant, Struan F. A. ; Leslie, R. David ; Phillips, David I. W. ; Trimble, Elisabeth R.</creator><creatorcontrib>Balcha, Shitaye A. ; Demisse, Abayneh G. ; Mishra, Rajashree ; Vartak, Tanwi ; Cousminer, Diana L. ; Hodge, Kenyaita M. ; Voight, Benjamin F. ; Lorenz, Kim ; Schwartz, Stanley ; Jerram, Samuel T. ; Gamper, Arla ; Holmes, Alice ; Wilson, Hannah F. ; Williams, Alistair J. K. ; Grant, Struan F. A. ; Leslie, R. David ; Phillips, David I. W. ; Trimble, Elisabeth R.</creatorcontrib><description>Aims/hypothesis
We aimed to characterise the immunogenic background of insulin-dependent diabetes in a resource-poor rural African community. The study was initiated because reports of low autoantibody prevalence and phenotypic differences from European-origin cases with type 1 diabetes have raised doubts as to the role of autoimmunity in this and similar populations.
Methods
A study of consecutive, unselected cases of recently diagnosed, insulin-dependent diabetes (
n
= 236, ≤35 years) and control participants (
n
= 200) was carried out in the ethnic Amhara of rural North-West Ethiopia. We assessed their demographic and socioeconomic characteristics, and measured non-fasting C-peptide, diabetes-associated autoantibodies and
HLA-DRB1
alleles. Leveraging genome-wide genotyping, we performed both a principal component analysis and, given the relatively modest sample size, a provisional genome-wide association study. Type 1 diabetes genetic risk scores were calculated to compare their genetic background with known European type 1 diabetes determinants.
Results
Patients presented with stunted growth and low BMI, and were insulin sensitive; only 15.3% had diabetes onset at ≤15 years. C-peptide levels were low but not absent. With clinical diabetes onset at ≤15, 16–25 and 26–35 years, 86.1%, 59.7% and 50.0% were autoantibody positive, respectively. Most had autoantibodies to GAD (GADA) as a single antibody; the prevalence of positivity for autoantibodies to IA-2 (IA-2A) and ZnT8 (ZnT8A) was low in all age groups. Principal component analysis showed that the Amhara genomes were distinct from modern European and other African genomes.
HLA-DRB1*03:01
(
p
= 0.0014) and
HLA-DRB1*04
(
p
= 0.0001) were positively associated with this form of diabetes, while
HLA-DRB1*15
was protective (
p
< 0.0001). The mean type 1 diabetes genetic risk score (derived from European data) was higher in patients than control participants (
p
= 1.60 × 10
−7
). Interestingly, despite the modest sample size, autoantibody-positive patients revealed evidence of association with SNPs in the well-characterised MHC region, already known to explain half of type 1 diabetes heritability in Europeans.
Conclusions/interpretation
The majority of patients with insulin-dependent diabetes in rural North-West Ethiopia have the immunogenetic characteristics of autoimmune type 1 diabetes. Phenotypic differences between type 1 diabetes in rural North-West Ethiopia and the industrialised world remain unexplained.</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-020-05229-x</identifier><identifier>PMID: 32705316</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adolescent ; Adult ; Age of Onset ; Autoantibodies ; Autoantibodies - immunology ; Autoimmunity ; Black People - genetics ; C-Peptide - blood ; Child ; Diabetes ; Diabetes mellitus (insulin dependent) ; Diabetes Mellitus, Type 1 - genetics ; Diabetes Mellitus, Type 1 - immunology ; Drb1 protein ; Ethiopia ; Female ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Genotyping ; Glutamate decarboxylase ; Heritability ; Histocompatibility antigen HLA ; HLA-DRB1 Chains - genetics ; Human Physiology ; Humans ; Immunogenetics ; Immunogenicity ; Insulin ; Internal Medicine ; Major histocompatibility complex ; Male ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Peptides ; Population studies ; Principal Component Analysis ; Principal components analysis ; Single-nucleotide polymorphism ; Young Adult ; Zinc Transporter 8 - immunology</subject><ispartof>Diabetologia, 2020-10, Vol.63 (10), p.2158-2168</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-7011bf669226a9091099a29d34863793750fa6288023dba60c0d55e4621f428b3</citedby><cites>FETCH-LOGICAL-c474t-7011bf669226a9091099a29d34863793750fa6288023dba60c0d55e4621f428b3</cites><orcidid>0000-0002-7385-0415</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-020-05229-x$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-020-05229-x$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,777,781,882,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32705316$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Balcha, Shitaye A.</creatorcontrib><creatorcontrib>Demisse, Abayneh G.</creatorcontrib><creatorcontrib>Mishra, Rajashree</creatorcontrib><creatorcontrib>Vartak, Tanwi</creatorcontrib><creatorcontrib>Cousminer, Diana L.</creatorcontrib><creatorcontrib>Hodge, Kenyaita M.</creatorcontrib><creatorcontrib>Voight, Benjamin F.</creatorcontrib><creatorcontrib>Lorenz, Kim</creatorcontrib><creatorcontrib>Schwartz, Stanley</creatorcontrib><creatorcontrib>Jerram, Samuel T.</creatorcontrib><creatorcontrib>Gamper, Arla</creatorcontrib><creatorcontrib>Holmes, Alice</creatorcontrib><creatorcontrib>Wilson, Hannah F.</creatorcontrib><creatorcontrib>Williams, Alistair J. K.</creatorcontrib><creatorcontrib>Grant, Struan F. A.</creatorcontrib><creatorcontrib>Leslie, R. David</creatorcontrib><creatorcontrib>Phillips, David I. W.</creatorcontrib><creatorcontrib>Trimble, Elisabeth R.</creatorcontrib><title>Type 1 diabetes in Africa: an immunogenetic study in the Amhara of North-West Ethiopia</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis
We aimed to characterise the immunogenic background of insulin-dependent diabetes in a resource-poor rural African community. The study was initiated because reports of low autoantibody prevalence and phenotypic differences from European-origin cases with type 1 diabetes have raised doubts as to the role of autoimmunity in this and similar populations.
Methods
A study of consecutive, unselected cases of recently diagnosed, insulin-dependent diabetes (
n
= 236, ≤35 years) and control participants (
n
= 200) was carried out in the ethnic Amhara of rural North-West Ethiopia. We assessed their demographic and socioeconomic characteristics, and measured non-fasting C-peptide, diabetes-associated autoantibodies and
HLA-DRB1
alleles. Leveraging genome-wide genotyping, we performed both a principal component analysis and, given the relatively modest sample size, a provisional genome-wide association study. Type 1 diabetes genetic risk scores were calculated to compare their genetic background with known European type 1 diabetes determinants.
Results
Patients presented with stunted growth and low BMI, and were insulin sensitive; only 15.3% had diabetes onset at ≤15 years. C-peptide levels were low but not absent. With clinical diabetes onset at ≤15, 16–25 and 26–35 years, 86.1%, 59.7% and 50.0% were autoantibody positive, respectively. Most had autoantibodies to GAD (GADA) as a single antibody; the prevalence of positivity for autoantibodies to IA-2 (IA-2A) and ZnT8 (ZnT8A) was low in all age groups. Principal component analysis showed that the Amhara genomes were distinct from modern European and other African genomes.
HLA-DRB1*03:01
(
p
= 0.0014) and
HLA-DRB1*04
(
p
= 0.0001) were positively associated with this form of diabetes, while
HLA-DRB1*15
was protective (
p
< 0.0001). The mean type 1 diabetes genetic risk score (derived from European data) was higher in patients than control participants (
p
= 1.60 × 10
−7
). Interestingly, despite the modest sample size, autoantibody-positive patients revealed evidence of association with SNPs in the well-characterised MHC region, already known to explain half of type 1 diabetes heritability in Europeans.
Conclusions/interpretation
The majority of patients with insulin-dependent diabetes in rural North-West Ethiopia have the immunogenetic characteristics of autoimmune type 1 diabetes. Phenotypic differences between type 1 diabetes in rural North-West Ethiopia and the industrialised world remain unexplained.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age of Onset</subject><subject>Autoantibodies</subject><subject>Autoantibodies - immunology</subject><subject>Autoimmunity</subject><subject>Black People - genetics</subject><subject>C-Peptide - blood</subject><subject>Child</subject><subject>Diabetes</subject><subject>Diabetes mellitus (insulin dependent)</subject><subject>Diabetes Mellitus, Type 1 - genetics</subject><subject>Diabetes Mellitus, Type 1 - immunology</subject><subject>Drb1 protein</subject><subject>Ethiopia</subject><subject>Female</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genotyping</subject><subject>Glutamate decarboxylase</subject><subject>Heritability</subject><subject>Histocompatibility antigen HLA</subject><subject>HLA-DRB1 Chains - genetics</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Immunogenetics</subject><subject>Immunogenicity</subject><subject>Insulin</subject><subject>Internal Medicine</subject><subject>Major histocompatibility complex</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Peptides</subject><subject>Population studies</subject><subject>Principal Component Analysis</subject><subject>Principal components analysis</subject><subject>Single-nucleotide polymorphism</subject><subject>Young Adult</subject><subject>Zinc Transporter 8 - immunology</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kUuLFDEUhYMoTjv6B1xIwM1sojePSiouhGYYHzDoZnzsQqoq1ZWhK2mTlEz_e9P2OD4WQuAuzndP7uEg9JTCCwqgXmYAyhoCDAg0jGlycw-tqOCMgGDtfbQ66IS28usJepTzNQDwRsiH6IQzBQ2ncoU-X-13DlM8eNu54jL2Aa_H5Hv7CtuA_TwvIW5ccMX3OJdl2B-IMjm8niebLI4j_hBTmcgXlwu-KJOPO28fowej3Wb35Haeok9vLq7O35HLj2_fn68vSS-UKEQBpd0opWZMWg2agtaW6YGLVnKluWpgtJK1LTA-dFZCD0PTOCEZHWvEjp-i10ff3dLNbuhdKMluzS752aa9idabv5XgJ7OJ340SSmoqq8HZrUGK35Yawcw-9267tcHFJRsmmOJQDxEVff4Peh2XFGq8Sglo6mt1pdiR6lPMObnx7hgK5lCbOdZmam3mZ23mpi49-zPG3cqvnirAj0CuUti49Pvv_9j-ANAToVI</recordid><startdate>20201001</startdate><enddate>20201001</enddate><creator>Balcha, Shitaye A.</creator><creator>Demisse, Abayneh G.</creator><creator>Mishra, Rajashree</creator><creator>Vartak, Tanwi</creator><creator>Cousminer, Diana L.</creator><creator>Hodge, Kenyaita M.</creator><creator>Voight, Benjamin F.</creator><creator>Lorenz, Kim</creator><creator>Schwartz, Stanley</creator><creator>Jerram, Samuel T.</creator><creator>Gamper, Arla</creator><creator>Holmes, Alice</creator><creator>Wilson, Hannah F.</creator><creator>Williams, Alistair J. K.</creator><creator>Grant, Struan F. A.</creator><creator>Leslie, R. David</creator><creator>Phillips, David I. W.</creator><creator>Trimble, Elisabeth R.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7385-0415</orcidid></search><sort><creationdate>20201001</creationdate><title>Type 1 diabetes in Africa: an immunogenetic study in the Amhara of North-West Ethiopia</title><author>Balcha, Shitaye A. ; Demisse, Abayneh G. ; Mishra, Rajashree ; Vartak, Tanwi ; Cousminer, Diana L. ; Hodge, Kenyaita M. ; Voight, Benjamin F. ; Lorenz, Kim ; Schwartz, Stanley ; Jerram, Samuel T. ; Gamper, Arla ; Holmes, Alice ; Wilson, Hannah F. ; Williams, Alistair J. K. ; Grant, Struan F. A. ; Leslie, R. David ; Phillips, David I. W. ; Trimble, Elisabeth R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-7011bf669226a9091099a29d34863793750fa6288023dba60c0d55e4621f428b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age of Onset</topic><topic>Autoantibodies</topic><topic>Autoantibodies - immunology</topic><topic>Autoimmunity</topic><topic>Black People - genetics</topic><topic>C-Peptide - blood</topic><topic>Child</topic><topic>Diabetes</topic><topic>Diabetes mellitus (insulin dependent)</topic><topic>Diabetes Mellitus, Type 1 - genetics</topic><topic>Diabetes Mellitus, Type 1 - immunology</topic><topic>Drb1 protein</topic><topic>Ethiopia</topic><topic>Female</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Genotyping</topic><topic>Glutamate decarboxylase</topic><topic>Heritability</topic><topic>Histocompatibility antigen HLA</topic><topic>HLA-DRB1 Chains - genetics</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Immunogenetics</topic><topic>Immunogenicity</topic><topic>Insulin</topic><topic>Internal Medicine</topic><topic>Major histocompatibility complex</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Peptides</topic><topic>Population studies</topic><topic>Principal Component Analysis</topic><topic>Principal components analysis</topic><topic>Single-nucleotide polymorphism</topic><topic>Young Adult</topic><topic>Zinc Transporter 8 - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Balcha, Shitaye A.</creatorcontrib><creatorcontrib>Demisse, Abayneh G.</creatorcontrib><creatorcontrib>Mishra, Rajashree</creatorcontrib><creatorcontrib>Vartak, Tanwi</creatorcontrib><creatorcontrib>Cousminer, Diana L.</creatorcontrib><creatorcontrib>Hodge, Kenyaita M.</creatorcontrib><creatorcontrib>Voight, Benjamin F.</creatorcontrib><creatorcontrib>Lorenz, Kim</creatorcontrib><creatorcontrib>Schwartz, Stanley</creatorcontrib><creatorcontrib>Jerram, Samuel T.</creatorcontrib><creatorcontrib>Gamper, Arla</creatorcontrib><creatorcontrib>Holmes, Alice</creatorcontrib><creatorcontrib>Wilson, Hannah F.</creatorcontrib><creatorcontrib>Williams, Alistair J. K.</creatorcontrib><creatorcontrib>Grant, Struan F. A.</creatorcontrib><creatorcontrib>Leslie, R. David</creatorcontrib><creatorcontrib>Phillips, David I. W.</creatorcontrib><creatorcontrib>Trimble, Elisabeth R.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Balcha, Shitaye A.</au><au>Demisse, Abayneh G.</au><au>Mishra, Rajashree</au><au>Vartak, Tanwi</au><au>Cousminer, Diana L.</au><au>Hodge, Kenyaita M.</au><au>Voight, Benjamin F.</au><au>Lorenz, Kim</au><au>Schwartz, Stanley</au><au>Jerram, Samuel T.</au><au>Gamper, Arla</au><au>Holmes, Alice</au><au>Wilson, Hannah F.</au><au>Williams, Alistair J. K.</au><au>Grant, Struan F. A.</au><au>Leslie, R. David</au><au>Phillips, David I. W.</au><au>Trimble, Elisabeth R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Type 1 diabetes in Africa: an immunogenetic study in the Amhara of North-West Ethiopia</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2020-10-01</date><risdate>2020</risdate><volume>63</volume><issue>10</issue><spage>2158</spage><epage>2168</epage><pages>2158-2168</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis
We aimed to characterise the immunogenic background of insulin-dependent diabetes in a resource-poor rural African community. The study was initiated because reports of low autoantibody prevalence and phenotypic differences from European-origin cases with type 1 diabetes have raised doubts as to the role of autoimmunity in this and similar populations.
Methods
A study of consecutive, unselected cases of recently diagnosed, insulin-dependent diabetes (
n
= 236, ≤35 years) and control participants (
n
= 200) was carried out in the ethnic Amhara of rural North-West Ethiopia. We assessed their demographic and socioeconomic characteristics, and measured non-fasting C-peptide, diabetes-associated autoantibodies and
HLA-DRB1
alleles. Leveraging genome-wide genotyping, we performed both a principal component analysis and, given the relatively modest sample size, a provisional genome-wide association study. Type 1 diabetes genetic risk scores were calculated to compare their genetic background with known European type 1 diabetes determinants.
Results
Patients presented with stunted growth and low BMI, and were insulin sensitive; only 15.3% had diabetes onset at ≤15 years. C-peptide levels were low but not absent. With clinical diabetes onset at ≤15, 16–25 and 26–35 years, 86.1%, 59.7% and 50.0% were autoantibody positive, respectively. Most had autoantibodies to GAD (GADA) as a single antibody; the prevalence of positivity for autoantibodies to IA-2 (IA-2A) and ZnT8 (ZnT8A) was low in all age groups. Principal component analysis showed that the Amhara genomes were distinct from modern European and other African genomes.
HLA-DRB1*03:01
(
p
= 0.0014) and
HLA-DRB1*04
(
p
= 0.0001) were positively associated with this form of diabetes, while
HLA-DRB1*15
was protective (
p
< 0.0001). The mean type 1 diabetes genetic risk score (derived from European data) was higher in patients than control participants (
p
= 1.60 × 10
−7
). Interestingly, despite the modest sample size, autoantibody-positive patients revealed evidence of association with SNPs in the well-characterised MHC region, already known to explain half of type 1 diabetes heritability in Europeans.
Conclusions/interpretation
The majority of patients with insulin-dependent diabetes in rural North-West Ethiopia have the immunogenetic characteristics of autoimmune type 1 diabetes. Phenotypic differences between type 1 diabetes in rural North-West Ethiopia and the industrialised world remain unexplained.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>32705316</pmid><doi>10.1007/s00125-020-05229-x</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-7385-0415</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Diabetologia, 2020-10, Vol.63 (10), p.2158-2168 |
| issn | 0012-186X 1432-0428 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7476916 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Adolescent Adult Age of Onset Autoantibodies Autoantibodies - immunology Autoimmunity Black People - genetics C-Peptide - blood Child Diabetes Diabetes mellitus (insulin dependent) Diabetes Mellitus, Type 1 - genetics Diabetes Mellitus, Type 1 - immunology Drb1 protein Ethiopia Female Genome-wide association studies Genome-Wide Association Study Genomes Genotyping Glutamate decarboxylase Heritability Histocompatibility antigen HLA HLA-DRB1 Chains - genetics Human Physiology Humans Immunogenetics Immunogenicity Insulin Internal Medicine Major histocompatibility complex Male Medicine Medicine & Public Health Metabolic Diseases Peptides Population studies Principal Component Analysis Principal components analysis Single-nucleotide polymorphism Young Adult Zinc Transporter 8 - immunology |
| title | Type 1 diabetes in Africa: an immunogenetic study in the Amhara of North-West Ethiopia |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T13%3A22%3A19IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Type%201%20diabetes%20in%20Africa:%20an%20immunogenetic%20study%20in%20the%20Amhara%20of%20North-West%20Ethiopia&rft.jtitle=Diabetologia&rft.au=Balcha,%20Shitaye%20A.&rft.date=2020-10-01&rft.volume=63&rft.issue=10&rft.spage=2158&rft.epage=2168&rft.pages=2158-2168&rft.issn=0012-186X&rft.eissn=1432-0428&rft_id=info:doi/10.1007/s00125-020-05229-x&rft_dat=%3Cproquest_pubme%3E2440540589%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2440540589&rft_id=info:pmid/32705316&rfr_iscdi=true |