Background Diabetes and Hyperlipidemia are major risk factors for stroke across the world population. TCF7L2, a key player of the WNT signaling pathway shows genetic association with both metabolic disturbances. However, its role in stroke pathogenesis (if any) is not well characterized. Objectives Thus, here we aim to (a) examine and correlate dysregulation of TCF7L2 expression with diabetes or hyperlipidemia-associated Ischemic Stroke, (b) identify genetic risk variants in the TCF7L2 gene and (c) establish a correlation between TCF7L2 mRNA expressions with biochemical parameters. Methods Based on radiological findings for Ischemic Stroke, a total of 50 unrelated subjects were recruited with diverse biochemical parameters for TCF7L2 mRNA expression study in PBMC, followed by correlation with fasting blood sugar and lipid profile. Furthermore, mutation screening and genetic association studies (rs7901695 & rs7903146) were performed among 326 cases and 258 controls from India. Results Here, we observed a significant downregulation of TCF7L2 gene expression among hyperlipidemic stroke patients than cases and control without dyslipidemia but no change between the cases with different diabetic statuses. Moreover, a strong negative correlation between TCF7L2 mRNA level and total blood cholesterol but not for FBS was identified. The rs7901695T/C appeared as a promising genetic risk factor for stroke among eastern Indians. Conclusion Therefore, we can suggest that alteration in TCF7L2 leading to stroke pathogenesis is more associated with hyperlipidemia than diabetes among Indians. Its expression level in PBMC is influenced by rs7901695T/C and holds a good promise to be used as a diagnostic marker.

The authors have declared no competing interest.

Supported by grants from the Department of Science & Technology, Govt. of India, under to DS WISE-PDF Programme (DST-WISE-PDF/LS-1/2024) and Cognitive Science Research Initiative Programme (DST/CSRI-P/2017/22), and Department of Biotechnology, Ministry of Science & Technology, Govt. of India to AB and SG (BT/NIDAN/01/05/2018).

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the National Neurosciences Centre Calcutta, Kolkata, India, Nil Ratan Sircar Medical College & Hospital, Kolkata, India and Shree Krishna Hospital, Pramukhswami Medical College, Karamsad, Gujrat, India. The Ethics Committees of the abovementioned Institutes approved the study protocol.

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