Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder caused by genetic, environmental and immunological factors. It is known that neural development processes are affected by immune func...

HIV, which causes acquired immune deficiency syndrome (AIDS), invades the host cell via the CD4 receptor and CCR5 or CXCR4 co-receptors. Interferons induced early in HIV infection induce an antiviral defense mechanism through IFNAR signaling. Our study aimed to examine the relationship between CCR5, CXCR4, and IFNAR1 gene variations as a risk factor in HIV + patients and their response to their clinical parameters. Targeted next-generation sequencing (tNGS) was used to perform molecular genotyping analysis of the CCR5, CXCR4, and IFNAR1 genes in genomic DNA from 22 HIV + patients and 25 healthy individuals as controls. We detected 13 rare mutations in the study, including 3 missense, 1 synonymous, 2 5′UTR, 4 3′UTR, and 1 frameshift variation. We also analyzed 6 common variants in the IFNAR1 and CXCR4 genes. HIV + patients carrying the homozygous TT genotype of the IFNAR1 intronic rs2856973:T > A variant had higher CD4 + T cell counts compared with patients carrying the TA + AA genotypes of the rs2856973 variant in the naive and first month of the ART (p = 0.001 and p = 0.001, respectively). Similarly, participants receiving ART with a TT genotype of rs2856973:T > A showed a significantly higher CD4 + T cell count in the third month (p = 0.001). Patients carrying the homozygous wild-type genotype of the CXCR4 intronic rs2680880:A > T SNP had lower CD4 + T cell count compared with subjects carrying the AT + TT mutant genotypes of rs2680880:A > T in the naive and first-month period (p = 0.015 and p = 0.025, respectively). Our results demonstrate that intronic variations in the IFNAR1 rs2856973:T > A and CXCR4 rs2680880:A > T genes can contribute to modifications in HIV progression and CD4 + T recovery under ART.

Introduction: Epilepsy is a chronic neurological disorder characterized by recurrent seizures, with variants in ion channel genes such as SCN1A, SCN1B, and CACNA2D2 implicated in neuronal excitability. This research aims to explore genetic polymorphisms in the SCN1A, SCN1B, and CACNA2D2 genes among Turkish epilepsy patients and assess their impact on responsiveness to anti-seizure medications (ASMs). Methods: Targeted next-generation sequencing (tNGS) was applied to genomic DNA from 29 patients. Results: Common 15 variants were analyzed in CACNA2D2 (rs2239801, rs56287038), SCN1A (rs2298771, rs3032638, rs11394960, rs67636132, rs566839, rs1461193, rs6432861, rs2020318), and SCN1B (rs72556351, rs2278995, rs557140301, rs67701503, rs55742440). A statistically significant difference in ASM response was observed in the recessive model of SCN1A rs2298771: C>T (TT vs. CC+CT) (p = 0.044), with the TT genotype associated with improved response. CACNA2D2 rs56287038:G>T showed significance in the allelic model (p = 0.012); the T allele was found only in resistant patients. SCN1A haplotype analysis revealed reduced C allele frequency in responders (p = 0.041). The CT (rs2298771+rs2020318), CG (rs2298771+rs1461193), and CC (rs2298771+rs6432861) haplotypes also showed considerable differences among groups (p = 0.041, p = 0.023, p = 0.041, respectively). Moreover, CTG (rs2298771+rs2020318+rs1461193), CCG (rs2298771+rs6432861+rs1461193), and CTCG (rs2298771+rs2020318+rs6432861+rs1461193) haplotypes were significantly associated with treatment response (p = 0.023, p = 0.023, p = 0.022). However, none of these associations remained statistically significant after false discovery rate correction, and all findings should therefore be interpreted as exploratory. Conclusion: CACNA2D2 rs56287038:G>T and SCN1A rs2298771:C>T may effect ASM response.