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<p>The receptor for Advanced Glycation End Products (RAGE) gene polymorphism influences matrix metalloproteinase 9 (MMP-9) levels and its expression, but their genetic impact on the risk of nephropathy in type 2 Diabetes Mellitus remains unexplored in the north Indian population. This study examined the role of RAGE and MMP-9 polymorphisms and their circulating level among type 2 Diabetes patients with nephropathy. The case-control study included 100 type 2 Diabetes patients with nephropathy and 100 healthy controls. Biochemical parameters were measured using a clinical chemistry analyzer, and RAGE and MMP-9 polymorphisms were genotyped using a pre-designed TaqMan 5′ nuclease assay and real-time PCR. The circulating levels of AGE, soluble RAGE, and MMP-9 were estimated using an enzyme-linked immunosorbent assay (ELISA). The MMP-9 and AGEs levels were significantly increased and sRAGE was decreased in DN compared to control. The rs184003 TT genotype and T allele of RAGE was associated with the risk of nephropathy (OR: 5.65 (1.5–21.1), <i>p</i> &lt; 0.014). The 1704G &gt; T, TT + GT genotypes showed increased levels of blood glucose, HbA1c, LDL, TC, TG and UACR compared to GG carrier The MMP-9, -1562&#xa0;C/T was not significantly associated with susceptibility to DN. However, TT + TC genotypes of MMP-9 showed increased blood glucose, HbA1c and SBP compared to CC carriers. Linear regression analysis showed that increased TAG (<i>P</i> = 0.046) and lower sRAGE (<i>P</i> = 0.001) levels were predictors of increased UACR. This study suggested that the TT genotype and T allele of rs184003 RAGE is associated with the risk of nephropathy in patients with T2DM. We also found that increased TAG and lower sRAGE levels were predictive factors for increased albuminuria in DN.</p> Graphical Abstract <p></p>

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Genetic Variation in the Receptor for Advanced Glycation End Product (1704G > T) and Matrix Metalloproteinase-9 (-1562 C/T) in Type 2 Diabetic Patients with Nephropathy in Western Rajasthan

  • 期刊论文

  • 发表日期：

    2025年8月12日

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  • Rathore Rani,
  • Nachimuthu Maithili Karpaga Selvi,
  • Gopalakrishnan Maya,
  • Banerjee Mithu,
  • Purohit Purvi,
  • Kamala Kanth Shukla

摘要

The receptor for Advanced Glycation End Products (RAGE) gene polymorphism influences matrix metalloproteinase 9 (MMP-9) levels and its expression, but their genetic impact on the risk of nephropathy in type 2 Diabetes Mellitus remains unexplored in the north Indian population. This study examined the role of RAGE and MMP-9 polymorphisms and their circulating level among type 2 Diabetes patients with nephropathy. The case-control study included 100 type 2 Diabetes patients with nephropathy and 100 healthy controls. Biochemical parameters were measured using a clinical chemistry analyzer, and RAGE and MMP-9 polymorphisms were genotyped using a pre-designed TaqMan 5′ nuclease assay and real-time PCR. The circulating levels of AGE, soluble RAGE, and MMP-9 were estimated using an enzyme-linked immunosorbent assay (ELISA). The MMP-9 and AGEs levels were significantly increased and sRAGE was decreased in DN compared to control. The rs184003 TT genotype and T allele of RAGE was associated with the risk of nephropathy (OR: 5.65 (1.5–21.1), p < 0.014). The 1704G > T, TT + GT genotypes showed increased levels of blood glucose, HbA1c, LDL, TC, TG and UACR compared to GG carrier The MMP-9, -1562 C/T was not significantly associated with susceptibility to DN. However, TT + TC genotypes of MMP-9 showed increased blood glucose, HbA1c and SBP compared to CC carriers. Linear regression analysis showed that increased TAG (P = 0.046) and lower sRAGE (P = 0.001) levels were predictors of increased UACR. This study suggested that the TT genotype and T allele of rs184003 RAGE is associated with the risk of nephropathy in patients with T2DM. We also found that increased TAG and lower sRAGE levels were predictive factors for increased albuminuria in DN.

Graphical Abstract