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Evaluation of Apolipoprotein e4 allele as susceptible factor for neurodegenerative diseases among Eastern Indians

SADHUKHAN, D.; MISHRA, S.; MUKHERJEE, P.; BISWAS, A.; HUI, S. P.; BANERJEE, T. K.; BISWAS, A.

2023-06-22 genetic and genomic medicine
10.1101/2023.06.21.23291697 medRxiv
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IntroductionApolipoprotein E (ApoE) and age have been identified as the major risk factors for several neurodegenerative disorders. Among the three major isoforms (ApoE2, ApoE3 & ApoE4) of APOE, ApoE4 often shows ethnicity dependent association with neurodegenerative diseases. In the present study, we aim to determine the e4 allele/genotype frequency among the different neurodegenerative disorders and their correlation with several demographic and clinical parameters from eastern India. Material & MethodsA total of 826 individuals were recruited for this study which includes 128 PD-MCI, 144 PDD, 90 DLB, 114 FTD, 94 AD and 256 unrelated neurologically controls from eastern India. Subjects were analysed for APOE genotype (E2, E3 and E4) by PCR-RFLP techniques and Sanger sequencing. ResultsThe APOE4 allele was significantly associated with each of the disease subtypes, selected for the study (P = 0.016 to 0.000), while e3 allele was predominant among controls. Further stratification of subjects identified significant overrepresentation of (a) positive family history for FTD (P = 0.0414) & AD (P = 0.029) and (b) early age at onset of for PDD (P = 0.0316) and FTD (P = 0.0034) among the e4 allele carriers. Furthermore, lowering of BMSE score was also observed among the e4 allele carriers of AD subjects (P = 0.0324). ConclusionThere is a significant association of APOE4 allele with different neurodegenerative diseases influencing lowering of age at onset, BMSE score and positive family history among ethnic Bengali population of eastern India.

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