Frequency distribution of PRNP polymorphisms in the Pakistani population

Area of Science:

• Neurogenetics
• Molecular Biology
• Epidemiology

Background:

• Prion diseases stem from misfolded prion protein (PrPC to PrPSc).
• The M129V polymorphism in the prion protein gene (PRNP) influences susceptibility and disease phenotype in human prion diseases.
• No data on prion disorders or PRNP gene variations existed for the Pakistani population.

Purpose of the Study:

• To explore the genetic susceptibility of the Pakistani population to Creutzfeldt-Jakob disease (CJD).
• To determine the frequencies of M129V polymorphism and octapeptide repeat insertions/deletions (OPRIs/OPRDs) in the PRNP gene within Pakistan.

Main Methods:

• Screened 909 unrelated individuals from Pakistan for PRNP gene variations.
• Utilized Polymerase Chain Reaction coupled with Restriction Fragment Length Polymorphism (PCR-RFLP).
• Confirmed results with dideoxy automated Sanger sequencing for selected samples.

Main Results:

• Allelic frequencies for M129V were 0.7101 (129M) and 0.2899 (129V).
• Genotypic frequencies were 52.70% (129MM), 36.63% (129MV), and 10.67% (129VV).
• Observed OPRIs/OPRDs, including a 3-OPRI linked to the 129M allele; frequencies differed significantly from East Asian and Western populations.

Conclusions:

• The Pakistani population exhibits PRNP gene variations, including combined 129MM and 129VV homozygosity and OPRIs, suggesting susceptibility to prion disorders.
• The findings indicate potential cases of prion disorders in Pakistan, possibly with lower prevalence than in countries with higher life expectancy.
• Genetic variation data from individuals with single-gene disorders, like hemophiliacs, can serve as reliable population samples for genetic studies.