Increased susceptibility to Kuru of carriers of the PRNP 129 methionine/methionine genotype.
Kuru reached epidemic proportions by the mid-twentieth century among the Fore people of New Guinea and disappeared after the abolition of cannibalistic rituals. To determine susceptibility to kuru and its role in the spread and elimination of the epidemic, we analyzed the PRNP gene coding sequences in 5 kuru patients; no germline mutations were found. Analysis of the PRNP 129 methionine (M)/valine (V) polymorphism in 80 patients and 95 unaffected controls demonstrated that the kuru epidemic preferentially affected individuals with the M/M genotype. A higher representation of M/M carriers was observed among the affected young Fore males entering the age of risk, whereas a lower frequency of M/M homozygotes was found among the survivors. M/V and V/V genotypes predisposed to a lower risk of disease development and longer incubation times. These findings are relevant to the current outbreak of variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom, because all vCJD patients tested thus far have been M/M carriers.
Lee
H S
HS
Clinical Neurogenetics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Brown
P
P
Cervenáková
L
L
Garruto
R M
RM
Alpers
M P
MP
Gajdusek
D C
DC
Goldfarb
L G
LG
D000682:Amyloid / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003062:Codon; D004196:Disease Outbreaks; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007729:Kuru / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008715:Methionine / Q000235:genetics*; D009154:Mutation; D009512:New Guinea / Q000453:epidemiology; D011110:Polymorphism, Genetic; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors / Q000235:genetics*; D017422:Sequence Analysis, DNA
D000682:Amyloid; D003062:Codon; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors; D008715:Methionine