Laboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, Curitiba 81531-990, Paraná, Brazil.
Postgraduate Program in Genetics, Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, Curitiba 81531-990, Paraná, Brazil.
Genes (Basel). 2023 Apr 30;14(5):1026. doi: 10.3390/genes14051026.
Celiac disease (CD), despite its high morbidity, is an often-underdiagnosed autoimmune enteropathy. Using a modified version of the Brazilian questionnaire of the 2013 National Health Survey, we interviewed 604 Mennonites of Frisian/Flemish origin that have been isolated for 25 generations. A subgroup of 576 participants were screened for IgA autoantibodies in serum, and 391 participants were screened for HLA-DQ2.5/DQ8 subtypes. CD seroprevalence was 1:29 (3.48%, 95% CI = 2.16-5.27%) and biopsy-confirmed CD was 1:75 (1.32%, 95% CI = 0.57-2.59%), which is superior to the highest reported global prevalence (1:100). Half (10/21) of the patients did not suspect the disease. HLA-DQ2.5/DQ8 increased CD susceptibility (OR = 12.13 [95% CI = 1.56-94.20], = 0.003). The HLA-DQ2.5 carrier frequency was higher in Mennonites than in Brazilians ( = 7 × 10). HLA-DQ8 but not HLA-DQ2.5 carrier frequency differed among settlements ( = 0.007) and was higher than in Belgians, a Mennonite ancestral population ( = 1.8 × 10), and higher than in Euro-Brazilians ( = 6.5 × 10). The glutathione pathway, which prevents reactive oxygen species-causing bowel damage, was altered within the metabolic profiles of untreated CD patients. Those with lower serological positivity clustered with controls presenting close relatives with CD or rheumatoid arthritis. In conclusion, Mennonites have a high CD prevalence with a strong genetic component and altered glutathione metabolism that calls for urgent action to alleviate the burden of comorbidities due to late diagnosis.
乳糜泻（CD）尽管发病率高，但仍是一种常被漏诊的自身免疫性肠炎。我们采用了巴西 2013 年全国健康调查的改良问卷，对 604 名弗里斯兰/佛兰芒裔门诺派教徒进行了访谈，他们已经与世隔绝了 25 代。576 名参与者的血清中 IgA 自身抗体进行了筛查，391 名参与者筛查了 HLA-DQ2.5/DQ8 亚型。CD 的血清流行率为 1:29（3.48%，95%CI=2.16-5.27%），活检确诊的 CD 为 1:75（1.32%，95%CI=0.57-2.59%），优于全球报告的最高流行率（1:100）。一半（10/21）的患者没有怀疑这种疾病。HLA-DQ2.5/DQ8 增加了 CD 的易感性（OR=12.13[95%CI=1.56-94.20]， = 0.003）。HLA-DQ2.5 携带者的频率在门诺派教徒中高于巴西人（ = 7×10）。HLA-DQ8 而非 HLA-DQ2.5 携带者的频率在定居点之间存在差异（ = 0.007），高于比利时人（门诺派教徒的祖先），也高于欧裔巴西人（ = 6.5×10）。谷胱甘肽途径可防止活性氧引起的肠道损伤，在未经治疗的 CD 患者的代谢谱中发生了改变。那些血清学阳性率较低的患者与携带 CD 或类风湿关节炎的近亲的对照组聚类。总之，门诺派教徒的 CD 患病率较高，具有强烈的遗传成分和谷胱甘肽代谢改变，这呼吁采取紧急行动，以减轻因诊断延迟而导致的合并症负担。
