Analysis of Genotypes and Haplotypes of Factor VIII Gene Variants in Children with Hemophilia A from Northeast India

Introduction: Hemophilia A, an X-linked recessive disorder caused by deficient factor VIII activity, affects 1 in 5,000 males globally and in northern India. This bleeding disorder results from quantitative or qualitative abnormalities in FVIII. Previous Indian studies emphasize the significance of intron polymorphisms (IVS7-SNP, Bcl-I, and Hind-III) for carrier detection through linkage analysis. Using Amplification Refractory Mutation System (ARMS) primers, allele frequencies of IVS7 nt 27 G/A SNP, Bcl-I/intron 18, and Hind-III/intron 19 were analyzed in 205 unrelated Indian males with hemophilia, demonstrating the potential of these polymorphisms in carrier detection. Aim: The study analyzed the frequency of IVS7-SNP (G/A), rs4898352 (T/A) in intron 18 (Bcl-I), and rs4074307 (C/T) in intron 19 (Hind-III) using RFLP of the Factor VIII gene in hemophilia A patients from Uttar Pradesh and Bihar, India. Methods and Patients: Factor VIII assay was performed to diagnose each case. DNA was isolated from blood leukocytes, and genotyping was conducted using the PCR-Restriction Fragment Length Polymorphism method. All three polymorphisms—IVS7-SNP in intron 7, rs4898352 in intron 18, and rs4074307 in intron 19—were examined in 205 male children from 195 distinct families. Result: Intron7, Intron 18, and Intron 19 had a positive allele frequency of 0.10, 0.53, and 0.36. In contrast, the negative allele in Intron 7 had a higher prevalence for affected siblings than the positive allele. It was noted how many people in the lineage had hemophilia A and how many had died from problems associated with the disease. Conclusion: While heterozygosity rates were similar to those of children with hemophilia A across global ethnic groups, the frequency of three prevalent polymorphisms in Intron 7, introns 18, and Intron 19 was noted. The study offers valuable insights into carrier detection and genetic counseling in the Indian population, supporting early diagnosis and management strategies.