Institute for Inflammation Research, Center for Rheumatology and Spine Disease, Copenhagen University Hospital, Rigshospitalet, 2200 Copenhagen, Denmark.
Clinical Immunogenicity Analysis, Novo Nordisk A/S, 2760 Måløv, Denmark.
Int J Mol Sci. 2022 Jun 9;23(12):6481. doi: 10.3390/ijms23126481.
Single nucleotide polymorphisms (SNPs) in insulin and insulin receptor genes may influence the interaction between the two molecules, as may anti-insulin antibodies (IAs), commonly found in patients with type 1 diabetes mellitus (T1D) or type 2 diabetes mellitus (T2D) treated with exogenous insulin. We examined the impact of two SNPs in the human insulin gene (), rs3842752 and rs689, and two in the insulin receptor gene ( rs2245649 and rs2229429, on disease susceptibility, glycaemic control, and IAs formation in 100 T1D patients and 101 T2D patients treated with insulin. 79 individuals without diabetes were typed as healthy controls. The minor alleles of rs3842752 and rs689 in protected against T1D (OR: 0.50, = 0.01 and OR: 0.44; = 0.002, respectively). The minor alleles of both rs2245649 and rs2229429 in were risk factors for poor glycaemic control (HbA1c ≥ 80 mmol/mol) in T1D (OR: 5.35, = 0.009 and OR: 3.10, = 0.01, respectively). Surprisingly, the minor alleles of rs2245649 and rs2229429 in associated strongly with the absence of IAs in T1D (OR = 0.28, = 0.008 and OR = 0.30, = 0.002, respectively). In conclusion, the minor alleles of the investigated SNPs protect against T1D, and the minor alleles of the investigated SNPs are associated with poor glycaemic control and the absence of IAs in T1D.
胰岛素和胰岛素受体基因中的单核苷酸多态性(SNPs)可能会影响这两个分子之间的相互作用,而抗胰岛素抗体(IAs)通常存在于 1 型糖尿病(T1D)或 2 型糖尿病(T2D)患者中,这些患者接受外源性胰岛素治疗。我们研究了人类胰岛素基因中的两个 SNPs(rs3842752 和 rs689)以及胰岛素受体基因中的两个 SNPs(rs2245649 和 rs2229429)对 100 名 T1D 患者和 101 名接受胰岛素治疗的 T2D 患者的疾病易感性、血糖控制和 IAs 形成的影响。79 名无糖尿病个体被归类为健康对照。rs3842752 和 rs689 的次要等位基因可保护 T1D(OR:0.50, = 0.01 和 OR:0.44; = 0.002)。rs2245649 和 rs2229429 的次要等位基因在 T1D 中是血糖控制不佳(HbA1c≥80mmol/mol)的危险因素(OR:5.35, = 0.009 和 OR:3.10, = 0.01)。令人惊讶的是,rs2245649 和 rs2229429 的次要等位基因在 T1D 中与 IAs 的缺失密切相关(OR=0.28, = 0.008 和 OR=0.30, = 0.002)。总之,研究的 SNPs 的次要等位基因可预防 T1D,而研究的 SNPs 的次要等位基因与 T1D 患者的血糖控制不佳和 IAs 缺失有关。