Abstract
Background: Insulin-like growth factor-1 (IGF-1) has been demonstrated to increase fatty acid β oxidation during fasting, and play an important role in regulating lipid metabolism and type 2 diabetes mellitus (T2DM). The rs35767 (T > C) polymorphism, a functional SNP was found in IGF-1 promoter, which may directly affect IGF-1 expression. However, the inconsistent findings showed on the IGF-1 rs35767 polymorphism and T2DM risk. Methods: We performed a comprehensive meta-analysis to estimate the association between the IGF-1 rs35767 and T2DM risk among four genetic models (the allele, additive, recessive and dominant models). Results: A total 49,587 T2DM cases and 97,906 NDM controls were included in the allele model, a total 2256 T2DM cases and 2228 NDM controls were included in the other three genetic models (the additive; recessive and dominant models). In overall analysis, the IGF-1 rs35767 was shown to be significantly associated with increased T2DM risk for the allele model (T vs. C: OR = 1.251, 95% CI: 1.082–1.447, p = 0.002), additive model (homozygote comparisons: TT vs. CC: OR = 2.433, 95% CI: 1.095–5.405, p = 0.029; heterozygote comparisons: TC vs. CC: OR = 1.623, 95% CI: 1.055–2.495, p = 0.027) and dominant model (TT + CT vs. CC: OR = 1.934, 95% CI: 1.148–3.257, p = 0.013) with random effects model. After omitting Gouda’s study could reduce the heterogeneity, especially in the recessive model (TT vs. CC + CT: I2 = 38.7%, p = 0.163), the fixed effects model for recessive effect of the T allele (TT vs. CC + CT) produce results that were of borderline statistical significance (OR = 1.206, 95% CI: 1.004–1.448, p = 0.045). And increasing the risk of T2DM in Uyghur population of subgroup for the allele model. Conclusion: The initial analyses that included all studies showed statistically significant associations between the rs35767 SNP and type 2 diabetes, but after removing the Gouda et al. study produced results that were mostly not statistically significant. Therefore, there is not enough evidence from the results of the meta-analysis to indicate that the rs35767 SNP has a statistically significant association with type 2 diabetes.
Highlights
Diabetes is one of the most common chronic metabolic disorder diseases in the worldwide, over 90% of the diabetes patients are type 2 diabetes mellitus (T2DM), which is characterized by insulin resistance in peripheral tissues and dysregulated insulin secretion by pancreatic beta (β) cells (Banerjee and Vats, 2014; Song et al, 2015)
The Google Scholar, PubMed and Chinese National Knowledge Infrastructure were comprehensively searched for related studies published before July 31, 2021, using the key terms: “insulin-like growth factor 1 or Insulin-like growth factor-1 (IGF-1) or IGF1,” “rs35767 or rs35767 (T > C) or rs35767 (A > G),” “polymorphism or single-nucleotide polymorphisms (SNPs) or mutation or variant” and “diabetes or type 2 diabetes or T2DM.”
The results suggested that rs35767 was significantly related to the risk of T2DM in XinJiang, China subgroup (T vs. C: OR 1.508, 95% CI: 1.210–1.878, p 0.000) with fixed effects model; a random effects model were used to analyze the other provinces, China, rs35767 was shown no significant association with T2DM risk (T vs. C: OR 1.051, 95% CI: 0.943–1.173, p 0.369); and not a significantly associatied in the other countries subgroup (T vs. C: OR 0.975, 95% CI: 0.922–1.031, p 0.376) with fixed effects model (Figure 5)
Summary
Diabetes is one of the most common chronic metabolic disorder diseases in the worldwide, over 90% of the diabetes patients are type 2 diabetes mellitus (T2DM), which is characterized by insulin resistance in peripheral tissues and dysregulated insulin secretion by pancreatic beta (β) cells (Banerjee and Vats, 2014; Song et al, 2015). Studies have revealed lipid metabolismrelated genes and their single-nucleotide polymorphisms (SNPs) associated with insulin resistance and the development of T2DM (Ruchat et al, 2009; Dupuis et al, 2010; Chistiakov et al, 2012; Langberg et al, 2012; Mannino et al, 2013; Li et al, 2014; Thankamony et al, 2014; Yuan et al, 2015; Li et al, 2021). Insulin-like growth factor-1 (IGF-1) has been demonstrated to increase fatty acid β oxidation during fasting, and play an important role in regulating lipid metabolism and type 2 diabetes mellitus (T2DM). The inconsistent findings showed on the IGF-1 rs35767 polymorphism and T2DM risk
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