Polymorphisms of the PRNP gene in Chinese populations and the identification of a novel insertion mutation

Abstract

The two common polymorphisms (385A4G: M129V and 655G4A: E219 K) in the human prion gene (PRNP) play important roles in the pathogenesis of Creutzfeldt -Jakob diseases. We screened a total of 626 individuals, who represent three ethnic populations of China, Han, Hui, and Uyghur, for the two polymorphisms. The frequencies of M/M homozygote at residue 129 in these three groups differ significantly. The Han has a much higher frequency (98%) than Hui (85%) and Uyghur (60%). On the other hand, the frequencies of the E/E at residue 219 are higher in Uyghur (98%) and Hui (96%) than in Han (90%). We also investigated two other less common variants of PRNP, a silent substitution at residue 117 (351A4G: A117A), and one octapeptide-repeat deletion (1-OPRD) in the octapeptide-coding region. We found three Uyghur individuals with silent substitution at residue 117. Four Hui (2.0%) and one Han (0.5%) donors were found to be heterozygous for 1-OPRD. A novel three extra-repeat (72 bp) insertion within the octapeptide-coding region was identified in one healthy 11-years-old Hui. Identical mutation was also found in her mother but not her father.

No association of prion protein gene polymorphisms with Alzheimer's disease in Korean population

“…The M allele frequency is highest in Central and East Asia (＞ 90%), high in the Pacific (approximately 81%), in Europe (57-75%) and low (approximately 30%) in Native Americans (Palmer, ApoE-4 (-) (n = 306) ApoE-4 (+) (n = 181) 1991; Soldevila et al, 2003;Jeong et al, 2004;Yu et al, 2004;Lucotte and Mercier, 2005). Similarly, the MM genotype is highly abundant (＞ 93%) in East Asia.…”

Prion disease genetics

“…79,80 First and foremost among these is a polymorphism at PRNP codon 129 between methionine and valine, which has a strong disease susceptibility and phenotype modifying effect. 81 There are marked differences in codon 129 allele frequency worldwide: in the UK and Northern European population, the 129M allele frequency is around 0.65 with a slightly increasing cline through Europe into Africa 79,82 and a marked increasing cline through Asia, 67,83,84 129V is rare in Japan. 129V is the more frequent PRNP allele in only two regions: the Eastern Highlands of Papua New Guinea (PNG) at 0.55, and some Native American populations.…”

“…Small insertions have been detected incidentally or by population surveys. 67 It remains possible that small OPRI are neutral rare polymorphisms that CJD surveillance units will occasionally detect in elderly patients referred with otherwise sporadic CJD.…”

Complete sequence data support lack of balancing selection on PRNP in a natural Chinese population

“…They proposed that balancing selection played a critical role in shaping the worldwide distribution of 129V, including Fore-speaking New Guinean, African, European, and East Asian populations. In addition, it has been shown that the frequency of 129V in East Asians is low (Erginel-Unaltuna et al 2001;Jeong et al 2004;Yu et al 2004) and the Tajima's D is also lower, though positive, in East Asians than in other populations (Mead et al 2003). Kreitman and Di-Rienzo (2004) challenged the conclusions of Mead et al 2003 by pointing out that the exclusion of polymorphisms with low frequency may introduce ascertainment bias, which may tilt the estimation of the allele-frequency spectrum towards the strongly positive Tajima's D values seen in Mead's work.…”