Andrade Adriana de Souza, Bentes Aline Almeida, Diniz Lilian Martins, Hees Carvalho Silvia, Kroon Erna Geessien, Campos Marco Antonio
Instituto René Rachou, Fiocruz Minas, Belo Horizonte 30190-009, MG, Brazil.
Departamento de Pediatria, Universidade Federal de Minas Gerais, Belo Horizonte 30130-110, MG, Brazil.
Int J Mol Sci. 2025 Sep 1;26(17):8491. doi: 10.3390/ijms26178491.
The X-linked rs179008 T allele has been associated with altered antiviral immunity. Given their shared inflammatory pathways and higher pediatric mortality rates in Brazil during the pandemic, we investigated their association with multisystem inflammatory syndrome in children (MIS-C) together with Kawasaki disease (KS) following SARS-CoV-2 infection. A cross-sectional study (2021-2022) analyzed 73 hospitalized children (<13 years) with confirmed COVID-19. Genotyping for rs179008, (rs3764879, rs2407992), and rs3775291 was performed via PCR and Sanger sequencing. MIS-C/KS cases were identified using CDC criteria, with severity classified by the need for ICU care. Statistical analysis included Fisher's exact test and relative risk (RR) calculations. Hemizygous boys carrying the T allele had a 1.87-fold higher risk of MIS-C/KS ( = 0.007) and a 1.75-fold increased risk of severe or critical outcomes. The T allele frequency was 2.6× higher in MIS-C/KS cases versus other COVID-19 presentations. All fatalities occurred in boys (3/8 MIS-C cases) with one T-allele carrier. No associations were found for or variants. The rs179008 T allele is a potential genetic risk factor for severe post-COVID-19 inflammatory syndromes in boys, likely due to impaired immune signaling. These findings highlight its utility as a biomarker for risk stratification in pediatric populations.
X连锁的rs179008 T等位基因与抗病毒免疫改变有关。鉴于它们在炎症途径上的共性以及巴西在疫情期间较高的儿童死亡率，我们研究了它们与儿童多系统炎症综合征（MIS-C）以及新型冠状病毒2感染后的川崎病（KS）之间的关联。一项横断面研究（2021 - 2022年）分析了73名确诊为新冠肺炎的住院儿童（<13岁）。通过聚合酶链反应（PCR）和桑格测序对rs179008、（rs3764879、rs2407992）和rs3775291进行基因分型。使用美国疾病控制与预防中心（CDC）的标准确定MIS-C/KS病例，并根据是否需要重症监护病房（ICU）护理来分类病情严重程度。统计分析包括费舍尔精确检验和相对风险（RR）计算。携带T等位基因的半合子男孩患MIS-C/KS的风险高1.87倍（P = 0.007），出现严重或危急结果的风险增加1.75倍。MIS-C/KS病例中的T等位基因频率比其他新冠肺炎表现高2.6倍。所有死亡病例均为男孩（3/8例MIS-C病例），其中1例为T等位基因携带者。未发现与其他变体存在关联。rs179008 T等位基因可能是男孩新冠肺炎后严重炎症综合征的潜在遗传风险因素，可能是由于免疫信号受损所致。这些发现凸显了其作为儿科人群风险分层生物标志物的效用。
