Bouts of thiamine deficiency may occur in upwards of 80% of patients with alcoholism;114,115 however, only ≈13% of such individuals develop WKS,116 raising the possibility that a genetic predisposition to WKS may exist in some individuals.15 Some studies have shown that transketolase binds TPP less effectively in patients with WKS than in healthy controls.117,118 No consistent correlation, however, has been found between transketolase variants and thiamine deficiency.119 Other genetic loci or variants associated with WKS susceptibility include the X-linked transketolase-like 1 gene,120 the high-affinity thiamine transporter protein gene SLC19A2,121 the γ-aminobutyric acid A receptor subunit gene cluster on chromosome 5q33,122 and the aldehyde dehydrogenase-2 ADH21 allele.123 One possibility is that several genetic variants and environmental factors must be present to generate a WKS phenotype, which only becomes clinically relevant when an individual’s diet is deficient in thiamine.10
