El Helaly Rania Mostafa, Elzehery Rasha Rizk, El-Emam Ola Ali, El Domiaty Huda Ahmed, Elbohy Wesam Reda, Aboelenin Hadil Mohamed, Salem Nanees Abdel-Badie
Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Department of Pediatrics, Pediatric Nephrology Unit, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Pediatr Diabetes. 2021 Jun;22(4):567-576. doi: 10.1111/pedi.13201. Epub 2021 Apr 2.
Genetic and environmental factors have been implicated in etiopathogenesis and progression of type 1 diabetes mellitus (T1DM) and diabetic nephropathy (DN). Genetic association between interleukin-10 (IL-10) single nucleotide polymorphisms (SNPs) with T2DM and DN was recently established. We aimed to explore the potential genetic risk of IL-10 gene rs1518111 and rs3021094 SNPs in susceptibility to T1DM and DN.
Cross-sectional study included 140 T1DM children, of whom 74 had DN and 90 controls. IL-10 gene rs1518111 and rs3021094 SNP were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique of the extracted genomic DNA from participants. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to explore the association between IL-10 gene polymorphisms and the risk of T1DM and DN.
For rs1518111 SNP, AA genotype was associated with high risk of T1DM (OR = 4.53; CI = 2.11-9.74; p < 0.001), while A allele was associated with high risk of both T1DM (OR = 3.35; CI = 2.20-5.09; p < 0.001) and DN (OR = 2.36; CI = 1.27-4.38; p = 0.006). For rs3021094 SNP, AC genotype displayed lower risk to develop T1DM (OR = 0.35; CI = 0.13-0.94; p = 0.037), while A allele displayed higher risk to develop T1DM (OR = 1.69; CI = 1.11-2.56; p = 0.013). GA and AC haplotypes of rs1518111 and rs3021094 had lower ORs for having T1DM and DN, while GC had lower OR for having T1DM.
AA genotype and A allele of IL-10 rs1518111 SNP could be linked to increased risk for T1DM and DN among Egyptian children. None of rs3021094 genotypes or alleles displayed significant association with DN. GA and AC haplotypes could be protective against T1DM and DN susceptibility.
遗传和环境因素与1型糖尿病（T1DM）及糖尿病肾病（DN）的发病机制和进展有关。白细胞介素-10（IL-10）单核苷酸多态性（SNP）与2型糖尿病和DN之间的遗传关联最近已被证实。我们旨在探讨IL-10基因rs1518111和rs3021094 SNP在T1DM和DN易感性中的潜在遗传风险。
横断面研究纳入了１４０名T1DM儿童，其中７４名患有DN，９０名作为对照。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术对参与者提取的基因组DNA进行IL-10基因rs1518111和rs3021094 SNP基因分型。应用优势比（OR）和95％置信区间（CI）来探讨IL-10基因多态性与T1DM和DN风险之间的关联。
对于rs1518111 SNP，AA基因型与T1DM高风险相关（OR = 4.53；CI = 2.11-9.74；p <0.001），而A等位基因与T1DM（OR = 3.35；CI = 2.20-5.09；p <0.001）和DN（OR = 2.36；CI = 1.27-4.38；p = 0.006）的高风险相关。对于rs3021094 SNP，AC基因型发生T1DM的风险较低（OR = 0.35；CI = 0.13-0.94；p = 0.037），而A等位基因发生T1DM的风险较高（OR = 1.69；CI = 1.11-2.56；p = 0.013）。rs1518111和rs3021094的GA和AC单倍型发生T1DM和DN的OR较低，而GC发生T1DM的OR较低。
IL-10 rs1518111 SNP的AA基因型和A等位基因可能与埃及儿童T1DM和DN风险增加有关。rs3021094的基因型或等位基因均未显示与DN有显著关联。GA和AC单倍型可能对T1DM和DN易感性具有保护作用。
