AIM
The apolipoprotein E ε4 (APOE ε4) allele is a well-established genetic risk factor for Alzheimer's disease (AD), with a gene-dose effect, but its prevalence and clinical correlates in remain underexplored in South Asians. We examined APOE ε4 homozygosity and its clinical correlates in Indian cohort.
PATIENTS AND METHODS
We analyzed APOE genotype data from 393 patients with AD and 850 age-matched healthy controls from India. Variables included family history of dementia, age at onset, behavioral and psychological symptoms of dementia (BPSD), comorbidities (Diabetes and Hypertension), and severity on the Hindi Mental Status Examination (HMSE) and Clinical Dementia Rating (CDR) scale.
RESULTS
APOE ε4 allele frequency was higher in patients with AD (25%) than controls (9%); homozygosity was also more frequent among patients (5% vs 1%; X2 = 103.48, p < 0.001). Homozygosity was associated with family history of dementia, [Odds Ratio (OR) 4.03, 95% CI 1.46-11.10, p = 0.007], consistent on Firth analysis, but not with age at onset, duration, severity, BPSD, or comorbidities.
CONCLUSION
In this Indian cohort, APOE ε4 homozygosity reflects increased susceptibility and familial aggregation of AD but does not confer a more severe or distinct phenotype, suggesting ancestry- specific expression of APOE ε4 gene-dose effects.
Pratibha Vinod, C. Arampady, Somdatta Sen et al.· Neurodegenerative Disease Ma...· 0 citations
Background Alcohol dependence and cirrhosis are key outcomes of increased alcohol use, with genetic factors increasingly implicated. A functional promoter variant (rs361525) in the TNF-α gene may contribute to ALD pathogenesis, while a loss-of-function variant (rs58542926) in TM6SF2 modifies liver disease progression. We aimed to study these SNPs and assess DNA methylation at TM6SF2 loci in individuals with and without alcohol-related cirrhosis. Methods The study included men (N = 243) with alcohol dependence with cirrhosis (AUD-C+ve) and without cirrhosis (AUD-C-ve), based on ICD-10 criteria, recruited from SJMCH. Fibroscan and/or sonography (LSM < 14 kPa) ruled out severe fibrosis. Genotyping was performed for TNFα (rs361525) and TM6SF2 (rs58542926). Genomic DNA (N = 100) underwent bisulfite conversion followed by pyrosequencing at TM6SF2 loci. Methylation levels were calculated separately for individual CpG sites and as the mean of four CpG sites. Group differences were assessed using unpaired t-tests, and genetic models were applied based on risk allele status. Results Genotype and allele frequencies at both loci were comparable between AUD-C+ve and AUD-C–ve groups. TM6SF2 methylation was significantly reduced in the AUD-C+ve group (uncorrected p = 0.03). A trend was also noted for TNF-genotype with A-carriers having lower TM6SF2 global methylation levels (p = 0.06). We did not observe any differences in genotype and allele frequencies for both TM6SF2 and TNFα variants. Duration of alcohol consumption was significantly associated with TM6SF2 methylation (p = 0.02). Conclusion TM6SF2 hypomethylation in AUD-C+ve individuals may influence lipid metabolism and contribute to liver injury and HCC progression. Reduced methylation among TNF-α risk allele carriers suggests a potential gene–epigenetic interaction. Overall, higher alcohol exposure and genetic susceptibility may together predispose to worsening alcohol-related cirrhosis.
B. Shankarappa, J. Mahadevan, Pratima Murthy et al.· Frontiers in Medicine· 0 citations
