{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DEFA3, one of the genes encoding human neutrophil peptide 3 (HNP‐3), is a key component of the innate immune system that mediates host defense through its potent antimicrobial activity. Studies have shown that the DEFA3 locus, which along with DEFA1 forms part of a variable tandem array, exhibits extensive copy number variation that correlates with differential mRNA and peptide expression levels in circulating neutrophils."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Variation at this locus has been implicated in the modulation of inflammatory responses and susceptibility to infection‐related complications; for example, higher copy numbers of DEFA1/DEFA3 have been associated with altered plasma levels of HNPs and an increased risk of severe sepsis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, analyses in patients with diabetes indicate that while DEFA1/DEFA3 gene copy number does not directly predict circulating peptide levels, the elevated levels of α‐defensins observed in these patients may contribute to inflammatory processes and associated microvascular complications."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Population studies have further demonstrated that the absence of DEFA3 in a subset of individuals varies across ethnic groups, suggesting that differences in innate immune function driven by DEFA3 copy number polymorphism may influence disease predisposition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Altered expression of DEFA3 has also been observed in diverse pathological conditions. For instance, its dysregulated expression in salivary gland tumors may reflect immunological responses linked to tissue inflammation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", whereas during certain infections, such as those modulated by interleukin‐18, marked upregulation of DEFA3 (along with other α‐defensins) likely enhances mucosal antimicrobial activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In the context of genetic disorders, DEFA3 copy number has been considered a potential modifier influencing phenotypic variability, as seen in mitochondrial mutation–related hearing loss"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", and its enhanced expression has been noted in colorectal cancer tissues, suggesting a role in tumor-associated immune responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings demonstrate that DEFA3 functions as an antimicrobial peptide critical for innate immune defense and that its copy number variation and expression levels not only dictate local antimicrobial activity but also influence systemic inflammatory responses and disease susceptibility, including outcomes in sepsis and other complex disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Patricia M R Aldred, Edward J Hollox, John A L Armour "}, {"type": "b", "children": [{"type": "t", "text": "Copy number polymorphism and expression level variation of the human alpha-defensin genes DEFA1 and DEFA3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddi209"}], "href": "https://doi.org/10.1093/hmg/ddi209"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15944200"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15944200"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "QiXing Chen, Matthew Hakimi, ShuiJing Wu, et al. 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