{
  "id": "SCR-LIP-000240",
  "statement": "This review identifies specific lipedema-associated variants in AKR1C genes, including the familial AKR1C1 p.Leu213Gln (L213Q) mutation segregating across three generations and reducing catalytic efficiency ~50%, the gain-of-function AKR1C2 Ser320PheTer2 mutation, AKR1C2 overexpression in 24% (5/21) of patients without coding mutations, and regulatory SNPs rs28571848 (glucocorticoid receptor site) and rs34477787 (RORα site) that increase AKR1C2/AKR1C3 expression and truncal fat mass independent of BMI.",
  "statement_pt": "Esta revisão identifica variantes específicas associadas ao lipedema em genes AKR1C, incluindo a mutação familial AKR1C1 p.Leu213Gln (L213Q) que segrega em três gerações e reduz a eficiência catalítica em ~50%, a mutação de ganho de função AKR1C2 Ser320PheTer2, a superexpressão de AKR1C2 em 24% (5/21) dos pacientes sem mutações codificantes, e os polimorfismos regulatórios rs28571848 (sítio do receptor glucocorticoide) e rs34477787 (sítio RORα) que aumentam a expressão de AKR1C2/AKR1C3 e a massa gorda truncal independentemente do IMC.",
  "claim_type": "clinical_association",
  "context": {
    "population": "—",
    "condition": "lipedema",
    "exposure": "—",
    "comparator": "—",
    "outcome": "—",
    "scope": "auto-ingested from Layer 1 surveillance"
  },
  "knowledge_state": "emerging",
  "evidence_confidence": "low",
  "evidence": [
    {
      "ref": "DOI:10.4081/vl.2026.15495",
      "stance": "supporting",
      "study_design": "review",
      "n": null,
      "risk_of_bias": "unknown",
      "grade": "low",
      "year": 2026,
      "amato_authored": false,
      "note": "The article directly reviews specific genetic variants and inheritance patterns in lipedema (familial AKR1C1 L213Q segregating in 3 generations, AKR1C2 mutation, regulatory SNPs), proposing a mono-to-multifactorial genetic model. As a narra",
      "title": "From rare familial mutations to multifactorial disease: aldo-keto reductase 1C enzymes as a central biological pathway in lipedema",
      "authors": "Vainberg et al.",
      "journal": "Veins and Lymphatics"
    }
  ],
  "relations": [],
  "gaps": "Auto-ingested single source; not yet human-reviewed.",
  "primary_amato_source": null,
  "curators": [],
  "provenance": {
    "auto": true,
    "engine": "anthropic/claude-opus-4.8",
    "question": "SQ-LIP-000025",
    "source": "library",
    "ingested": "2026-05-31"
  },
  "created": "2026-05-31",
  "updated": "2026-05-31",
  "history": [
    {
      "date": "2026-05-31",
      "event": "created",
      "detail": "auto-ingested for SQ-LIP-000025"
    }
  ],
  "license": "CC-BY-4.0",
  "answers_questions": [
    {
      "id": "SQ-LIP-000025",
      "role": "supporting",
      "question": "What specific genetic variants or inheritance patterns have been identified in lipedema?",
      "url": "https://scientificclaims.org/q/SQ-LIP-000025.html"
    }
  ],
  "url": "https://scientificclaims.org/c/SCR-LIP-000240.html"
}