Influence of Insulin Receptor Single Nucleotide Polymorphisms on Glycaemic Control and Formation of Anti-Insulin Antibodies in Diabetes Mellitus
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....
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/12/6481 |
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| author | Laura Massarenti Christina Aniol-Nielsen Christian Enevold Henrik Toft-Hansen Claus Henrik Nielsen |
| author_facet | Laura Massarenti Christina Aniol-Nielsen Christian Enevold Henrik Toft-Hansen Claus Henrik Nielsen |
| author_sort | Laura Massarenti |
| collection | DOAJ |
| description | 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 (<i>INS</i>), rs3842752 and rs689, and two in the insulin receptor gene (<i>INSR)</i> 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 <i>INS</i> protected against T1D (OR: 0.50, <i>p</i> = 0.01 and OR: 0.44; <i>p</i> = 0.002, respectively). The minor alleles of both rs2245649 and rs2229429 in <i>INSR</i> were risk factors for poor glycaemic control (HbA1c ≥ 80 mmol/mol) in T1D (OR: 5.35, <i>p</i> = 0.009 and OR: 3.10, <i>p</i> = 0.01, respectively). Surprisingly, the minor alleles of rs2245649 and rs2229429 in <i>INSR</i> associated strongly with the absence of IAs in T1D (OR = 0.28, <i>p</i> = 0.008 and OR = 0.30, <i>p</i> = 0.002, respectively). In conclusion, the minor alleles of the investigated <i>INS</i> SNPs protect against T1D, and the minor alleles of the investigated <i>INSR</i> SNPs are associated with poor glycaemic control and the absence of IAs in T1D. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:35:54Z |
| publishDate | 2022-06-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4ae94af3b2404cc59d6e266d2e6ccaf72023-11-23T17:01:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012312648110.3390/ijms23126481Influence of Insulin Receptor Single Nucleotide Polymorphisms on Glycaemic Control and Formation of Anti-Insulin Antibodies in Diabetes MellitusLaura Massarenti0Christina Aniol-Nielsen1Christian Enevold2Henrik Toft-Hansen3Claus Henrik Nielsen4Institute for Inflammation Research, Center for Rheumatology and Spine Disease, Copenhagen University Hospital, Rigshospitalet, 2200 Copenhagen, DenmarkInstitute for Inflammation Research, Center for Rheumatology and Spine Disease, Copenhagen University Hospital, Rigshospitalet, 2200 Copenhagen, DenmarkInstitute for Inflammation Research, Center for Rheumatology and Spine Disease, Copenhagen University Hospital, Rigshospitalet, 2200 Copenhagen, DenmarkImmunogenicity Assay Development, Novo Nordisk A/S, 2760 Måløv, DenmarkInstitute for Inflammation Research, Center for Rheumatology and Spine Disease, Copenhagen University Hospital, Rigshospitalet, 2200 Copenhagen, DenmarkSingle 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 (<i>INS</i>), rs3842752 and rs689, and two in the insulin receptor gene (<i>INSR)</i> 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 <i>INS</i> protected against T1D (OR: 0.50, <i>p</i> = 0.01 and OR: 0.44; <i>p</i> = 0.002, respectively). The minor alleles of both rs2245649 and rs2229429 in <i>INSR</i> were risk factors for poor glycaemic control (HbA1c ≥ 80 mmol/mol) in T1D (OR: 5.35, <i>p</i> = 0.009 and OR: 3.10, <i>p</i> = 0.01, respectively). Surprisingly, the minor alleles of rs2245649 and rs2229429 in <i>INSR</i> associated strongly with the absence of IAs in T1D (OR = 0.28, <i>p</i> = 0.008 and OR = 0.30, <i>p</i> = 0.002, respectively). In conclusion, the minor alleles of the investigated <i>INS</i> SNPs protect against T1D, and the minor alleles of the investigated <i>INSR</i> SNPs are associated with poor glycaemic control and the absence of IAs in T1D.https://www.mdpi.com/1422-0067/23/12/6481diabetesglycaemic controlanti-insulin antibodies (IAs) single nucleotide polymorphisms (SNPs)insulin receptor |
| spellingShingle | Laura Massarenti Christina Aniol-Nielsen Christian Enevold Henrik Toft-Hansen Claus Henrik Nielsen Influence of Insulin Receptor Single Nucleotide Polymorphisms on Glycaemic Control and Formation of Anti-Insulin Antibodies in Diabetes Mellitus International Journal of Molecular Sciences diabetes glycaemic control anti-insulin antibodies (IAs) single nucleotide polymorphisms (SNPs) insulin receptor |
| title | Influence of Insulin Receptor Single Nucleotide Polymorphisms on Glycaemic Control and Formation of Anti-Insulin Antibodies in Diabetes Mellitus |
| title_full | Influence of Insulin Receptor Single Nucleotide Polymorphisms on Glycaemic Control and Formation of Anti-Insulin Antibodies in Diabetes Mellitus |
| title_fullStr | Influence of Insulin Receptor Single Nucleotide Polymorphisms on Glycaemic Control and Formation of Anti-Insulin Antibodies in Diabetes Mellitus |
| title_full_unstemmed | Influence of Insulin Receptor Single Nucleotide Polymorphisms on Glycaemic Control and Formation of Anti-Insulin Antibodies in Diabetes Mellitus |
| title_short | Influence of Insulin Receptor Single Nucleotide Polymorphisms on Glycaemic Control and Formation of Anti-Insulin Antibodies in Diabetes Mellitus |
| title_sort | influence of insulin receptor single nucleotide polymorphisms on glycaemic control and formation of anti insulin antibodies in diabetes mellitus |
| topic | diabetes glycaemic control anti-insulin antibodies (IAs) single nucleotide polymorphisms (SNPs) insulin receptor |
| url | https://www.mdpi.com/1422-0067/23/12/6481 |
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