Ala67Thr mutation in the poliovirus receptor CD155 is a potential risk factor for vaccine and wild‐type paralytic poliomyelitis

Abstract

Poliovirus infections can be asymptomatic or cause severe paralysis. Why some individuals develop paralytic poliomyelitis is unknown, but a role for host genetic factors has been suggested. To investigate if a polymorphism, Ala67Thr, in the poliovirus receptor, which has been found to facilitate increased resistance against poliovirus-induced cell lysis and apoptosis, is associated with increased risk of paralytic poliomyelitis, poliovirus receptor genotyping was undertaken among Italian subjects with vaccine-associated (n = 9), or with wild-type paralytic poliomyelitis (n = 6), and control subjects (n = 71), using RFLP-PCR and pyrosequencing. Heterozygous poliovirus receptor Ala67Thr genotype was found in 13.3% of the patients with paresis and in 8.5% of the controls (Odds Ratio = 1.667). The frequency of Ala67Thr among the controls is in agreement with earlier published data. It is concluded that the Ala67Thr mutation in the poliovirus receptor is a possible risk factor for the development of vaccine-associated or paralytic poliomyelitis associated with wild-type virus.

Ala67Thr Mutation in the Human Polio Virus Receptor (PVR) Gene in Post-Polio Syndrome Patients

“…As per previous studies done on PVR receptor [20][21][22][23], A/A homozygosity was not found. There might be two possibilities, one could be the lethality of homozygous mutation and another possibility is homozygous mutations are rare and failed to achieve in investigated population.…”

The genetics of post-polio syndrome - much to be unravelled!

“…PVR gene polymorphism in patients with progressive muscular atrophy was reported by Saunderson et al in 20048. Later, Ala67Thr polymorphism in the PVR gene was reported to be a possible risk factor for the aetiology of poliomyelitis9. The heterozygous single nucleotide polymorphism (SNP) (Ala67Thr) in CD155 gene has been reported in healthy population (6.8 to 8.5%) and the incidence has been shown to be significantly higher in polio paresis (13.3%) and progressive muscular atrophy (20%) patients89.…”

“…Later, Ala67Thr polymorphism in the PVR gene was reported to be a possible risk factor for the aetiology of poliomyelitis9. The heterozygous single nucleotide polymorphism (SNP) (Ala67Thr) in CD155 gene has been reported in healthy population (6.8 to 8.5%) and the incidence has been shown to be significantly higher in polio paresis (13.3%) and progressive muscular atrophy (20%) patients89. Nandi and colleagues10 in this issues have reported development of an SNP assay to detect the single nucleotide substitution (GCGaACG) in CD155/PVR gene.…”

Assay for identification of heterozygous single-nucleotide polymorphism (Ala67Thr) in human poliovirus receptor gene

“…Saunderson et al 22 found significantly higher frequency of heterozygous Ala67Thr change in PVR in patients with progressive muscular atrophy than in controls. Kindberg et al 23 reported an increased risk of developing paralytic poliomyelitis in heterozygous individuals carrying the Ala67Thr mutation in PVR . Genetic predisposition to poliomyelitis due to heterozygous (Ala67Thr) has neither been supported nor refuted by case-control studies in other countries222324.…”

“…DNA sequencing and PCR followed by restriction fragment length polymorphism (RFLP) have been used, so far, to detect the single nucleotide polymorphism (SNP, GCG→ACG) in CD155/PVR gene23. Both these methods are slow and require processing to obtain final results.…”