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The association of rs1111875 in HHEX with type 2 diabetes: A comprehensive meta-analysis - International Journal of Diabetes in Developing Countries

Background T2DM is the prevailing form of diabetes, representing over 90% of all instances. It mainly arises from insulin resistance and irregular insulin production. As T2DM continues to rise, particularly in India, gaining insight into the genetic factors influencing the disease is essential. Objective To find out the association between the risk of T2DM and genetic variations in the HHEX gene, particularly the rs1111875 variant. Methods We conducted a meta-analysis to identify relevant studies through NCBI, Science Direct, and Google Scholar. Studies that examined the relationship between the listed SNPs and T2DM were case–control studies and offered enough information to calculate OR were included. Results The meta-analysis encompassed 11 studies involving 5030 controls and 5196 cases of T2DM, concentrating on the rs1111875 polymorphism of the HHEX gene. No significant associations were found between the HHEX polymorphisms across various genetic models. The p-values obtained were < 0.01 for the allele model (C vs T; OR: 0.74, 95% CI: 0.51–1.09, I2 = 97%), < 0.01 for the dominant model (CC + CT vs. TT; OR: 0.76, 95% CI: 0.43–1.32, I2 = 94%), and < 0.01 for the recessive model (TT vs. CT + CC; OR: 0.73, 95% CI: 0.47–1.11, I2 = 96%). In the over-dominant model (CT vs. CC + TT), an odds ratio of 1.09 (95% CI: 0.86–1.37, I2 = 83%) was reported, with a p-value < 0.01. Conclusion The rs1111875 polymorphism in the HHEX gene was not significantly linked to T2DM risk, thereby reducing the risk of disease that is likely to occur. This indicates that further evaluation is crucial to delve into the potential of HHEX as a biomarker for assessing risk and guiding targeted interventions to understand its underlying mechanisms better.