Salem Nanees A, Alwakeel Angi A, Abdel-Latif Mayada, Hendawy Shaimaa R, Korkor Mai S
Pediatric Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Sci Rep. 2025 Apr 8;15(1):12012. doi: 10.1038/s41598-025-94447-7.
Obesity represents a major global public-health problem during childhood and adolescence. The genetic contribution to obesity and its consequences is well-established. Variation in glucocorticoid (GC)-sensitivity can be partly explained by polymorphisms in GC receptor (GR) gene where NR3C1; Bcl1 rs41423247 and NR3C1 rs6198 single nucleotide polymorphisms (SNPs) have been linked to higher and lower GC sensitivity, respectively. We aimed to explore the potential association between the GR gene SNPs and risk of obesity in a cohort of Egyptian children. We included 100 pre-pubertal children; 60 obese children and 40 age-and sex-matched normal-weight controls. Bcl1 rs41423247 SNP was genotyped using PCR-restriction fragment length polymorphism technique and NR3C1 rs6198 SNP was genotyped using Real-time-PCR.In Bcl1 rs41423247, obese children had more frequent CG, GG genotypes and G allele compared to healthy controls (P = 0.039, 0.019 and 0.007 respectively). Moreover, insulin resistance was significantly higher in combined CG + GG group compared to CC group. On the contrary, no significant differences were found in genotypes, alleles frequencies or insulin resistance between obese and non-obese children in NR3C1 rs6198. GR Bcl1 rs41423247 gene polymorphism may play a role in genetic susceptibility to obesity that can be a future targeted therapy for obesity.
肥胖是儿童和青少年时期的一个主要全球公共卫生问题。肥胖及其后果的遗传因素已得到充分证实。糖皮质激素（GC）敏感性的差异部分可由GC受体（GR）基因的多态性来解释，其中NR3C1；Bcl1 rs41423247和NR3C1 rs6198单核苷酸多态性（SNP）分别与较高和较低的GC敏感性相关。我们旨在探讨埃及儿童队列中GR基因SNP与肥胖风险之间的潜在关联。我们纳入了100名青春期前儿童；60名肥胖儿童和40名年龄和性别匹配的正常体重对照。使用PCR-限制性片段长度多态性技术对Bcl1 rs41423247 SNP进行基因分型，使用实时PCR对NR3C1 rs6198 SNP进行基因分型。在Bcl1 rs41423247中，与健康对照相比，肥胖儿童的CG、GG基因型和G等位基因频率更高（分别为P = 0.039、0.019和0.007）。此外，CG + GG组合组的胰岛素抵抗明显高于CC组。相反，在NR3C1 rs6198中，肥胖和非肥胖儿童在基因型、等位基因频率或胰岛素抵抗方面未发现显著差异。GR Bcl1 rs41423247基因多态性可能在肥胖的遗传易感性中起作用，这可能是未来肥胖的靶向治疗方法。
