{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T04:11:19Z","timestamp":1784866279538,"version":"3.55.0"},"reference-count":38,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Immunopathol Pharmacol"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Type 1 diabetes mellitus (T1DM) is characterized by autoimmune destruction of insulin-producing pancreatic beta (\u03b2-) cells. Previous studies suggested an imbalance between and pro- and anti-inflammatory cytokines exacerbates T1DM development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We aimed to test the hypothesis that patients with T1DM carry a higher frequency of regulatory genes associated with low levels of the anti-inflammatory cytokines interleukin-4 (IL-4), its receptor (IL-4R), and interleukin-10 (IL-10).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Accordingly, we compared frequencies of five different single nucleotide polymorphisms (SNPs) in T1DM patients and healthy controls who had been typed for HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The frequencies of rs2070874 (IL-4) alleles C and T differed between T1DM patients and controls (\n                      <jats:sup>c<\/jats:sup>\n                      p = 0.0065), as did their codominant (\n                      <jats:sup>c<\/jats:sup>\n                      p = 0.026) and recessive (\n                      <jats:sup>c<\/jats:sup>\n                      p = 0.015) models. Increased frequencies were observed in T1DM patients for HLA alleles: DRB1*03 (pc &lt; 0.0013), DRB1*04 (\n                      <jats:sup>c<\/jats:sup>\n                      p = 0.0169), DQA1*03 (\n                      <jats:sup>c<\/jats:sup>\n                      p = 0.0222), DQA1*05 (\n                      <jats:sup>c<\/jats:sup>\n                      p &lt; 0.0006), DQB1*02 (\n                      <jats:sup>c<\/jats:sup>\n                      p = 0.0005), and DQB1*06 (\n                      <jats:sup>c<\/jats:sup>\n                      p &lt; 0.0005). And lower frequencies were observed for: DRB1*07 (\n                      <jats:sup>c<\/jats:sup>\n                      p = 0.0078), DRB1*11 (\n                      <jats:sup>c<\/jats:sup>\n                      p = 0.0013), DRB1*13 (\n                      <jats:sup>c<\/jats:sup>\n                      p &lt; 0.0364), DRB1*15 (\n                      <jats:sup>c<\/jats:sup>\n                      p &lt; 0.0013), DQA1*01 (\n                      <jats:sup>c<\/jats:sup>\n                      p &lt; 0.0006), and DQA1*02 (\n                      <jats:sup>c<\/jats:sup>\n                      p = 0.0348). Certain DRB1: DQA1: DQB1 haplotypes showed greater frequencies, including, 03:05:02 (p &lt; 0.0001) and 04:03:03 (p = 0.0017), whereas others showed lower frequencies, including, 07:02:02 (p = 0.0032), 11:05:03 (p = 0.0007), and 15:01:06 (p = 0.0002). Stratification for the above HLA haplotypes with rs2070874\u00a0C\/C exhibited no significant differences between T1DM patients overall and controls. However, when stratified for the vulnerable HLA haplotype (03:05:02\/04:03:03), young patients in whom T1DM began at \u226413 years had a higher frequency of the SNP (rs2070874\u00a0C\/C); a gene associated with low IL-4 production (p &lt; 0.024).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study suggests that possession of the rs2070874\u00a0C\/C genotype, which is associated with low production of IL-4, increases the risk of T1DM in young individuals carrying vulnerable HLA alleles\/haplotypes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03946320221090330","type":"journal-article","created":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T13:16:29Z","timestamp":1649682989000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Single nucleotide polymorphism rs 2070874 at Interleukin-4 is associated with increased risk of type 1 diabetes mellitus independently of human leukocyte antigens"],"prefix":"10.1177","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1945-4363","authenticated-orcid":false,"given":"Awad E","family":"Osman","sequence":"first","affiliation":[{"name":"Pathology and Clinical Laboratory Management Department, King Fahad Medical City, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imad","family":"Brema","sequence":"additional","affiliation":[{"name":"Obesity, Endocrine and Metabolism Center, King Fahad Medical City, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"AlQurashi","sequence":"additional","affiliation":[{"name":"Research Center, King Fahad Medical City, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Al-Jurayyan","sequence":"additional","affiliation":[{"name":"Pathology and Clinical Laboratory Management Department, King Fahad Medical City, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Bradley","sequence":"additional","affiliation":[{"name":"National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muaawia A","family":"Hamza","sequence":"additional","affiliation":[{"name":"Research Center, King Fahad Medical City, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,4,11]]},"reference":[{"key":"bibr1-03946320221090330","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-020-00443-4"},{"key":"bibr2-03946320221090330","doi-asserted-by":"publisher","DOI":"10.1007\/PL00002961"},{"key":"bibr3-03946320221090330","doi-asserted-by":"publisher","DOI":"10.1007\/BF02221682"},{"key":"bibr4-03946320221090330","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.23.10.1516"},{"key":"bibr5-03946320221090330","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/9408370"},{"key":"bibr6-03946320221090330","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0805398"},{"key":"bibr7-03946320221090330","doi-asserted-by":"publisher","DOI":"10.2337\/db14-1497"},{"key":"bibr8-03946320221090330","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1147"},{"key":"bibr9-03946320221090330","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a007807"},{"key":"bibr10-03946320221090330","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1122"},{"key":"bibr11-03946320221090330","doi-asserted-by":"publisher","DOI":"10.1111\/pedi.12597"},{"key":"bibr12-03946320221090330","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2016.03.007"},{"key":"bibr13-03946320221090330","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0313153"},{"key":"bibr14-03946320221090330","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.7.4458"},{"key":"bibr15-03946320221090330","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.v32.i1.30"},{"issue":"10","key":"bibr16-03946320221090330","first-page":"4686","volume":"159","author":"Cameron MJ","year":"1997","journal-title":"Journal of immunology"},{"key":"bibr17-03946320221090330","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200002000-00016"},{"key":"bibr18-03946320221090330","doi-asserted-by":"publisher","DOI":"10.1080\/08820139.2017.1416398"},{"key":"bibr19-03946320221090330","volume-title":"Cytokine Gene Polymorphism in Human Disease: On-Line Databases, Supplement 3. 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