A 5′ intronic splice site polymorphism leads to a null allele of the P2X7 gene in 1–2% of the Caucasian population

The P2X7 gene is important for the innate immune response but known polymorphisms do not explain all subjects with loss of P2X7 function. A splice site mutation (g → t) was found at position +1 of the first intron of the P2X7 gene in 7 of 336 Caucasians and 1 of 39 subjects of Indian ethnicity. All eight subjects were heterozygous for the uncommon 1513A → C polymorphism of the P2X7 gene. RT-PCR and sequencing showed the splice site mutation was on the 1513C allele in the Caucasians and on the 1513A allele in the Indian subject. The splice site mutation is an inherited polymorphism and gives rise to a P2X7 null allele in 1–2% of the Caucasian population.