Key result
Although initial analyses showed the IGF-1 rs35767 T allele was associated with increased type 2 diabetes risk (OR 1.251), this association became non-significant after removing one highly influential study.
Why the study?
Previous findings regarding the association between the functional IGF-1 promoter polymorphism rs35767 and type 2 diabetes mellitus risk have been inconsistent.
Is the IGF-1 rs35767 polymorphism associated with increased susceptibility to type 2 diabetes mellitus?
Meta-Analysis (n=147,493)
Is the IGF-1 rs35767 polymorphism associated with increased susceptibility to type 2 diabetes mellitus?
Odds Ratio: 1.251 (95% CI 1.082–1.447)
p-value: p=0.002
There is insufficient evidence to conclude that the IGF-1 rs35767 polymorphism is significantly associated with type 2 diabetes mellitus susceptibility after accounting for study heterogeneity.
No consistent IGF-1 rs35767–T2DM link after sensitivity analysis; leaves open need for larger, diverse validation studies.
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.
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Zeng et al. (2021) conducted a meta-analysis in Type 2 Diabetes Mellitus (n=147,493). IGF-1 rs35767 polymorphism (T allele) vs. C allele was evaluated on Type 2 Diabetes Mellitus susceptibility (allele model) (OR 1.251, 95% CI 1.082-1.447, p=0.002). Although initial analyses showed the IGF-1 rs35767 T allele was associated with increased type 2 diabetes risk (OR 1.251), this association became non-significant after removing one highly influential study.
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