Two missense variants, 5C>T (Pro2Leu) and 238A>G (Ile80Val), were identified in five unrelated patients with AD while no mutations were observed in patients with ALS or FTD.
Pro2Leu was not significantly associated with risk of ALS in our cohort, and no variants in untranslated or flanking regions of CHCHD2 were associated with risk of MSA or ALS.
Meta-analysis of our data with studies in the literature showed that p.Pro2Leu variants were associated with sporadic PD (OR 2.51, 95%CI 1.53 to 4.11, p = 0.0002), especially in Asian populations (OR 2.92, 95%CI 1.68 to 5.07, p = 0.0001).
Two single nucleotide variants (-9T>G and 5C>T) in CHCHD2 were confirmed to have different frequencies between sporadic Parkinson's disease and controls, with odds ratios of 2·51 (95% CI 1·48-4·24; p=0·0004) and 4·69 (1·59-13·83, p=0·0025), respectively.
Pro2 Leu, however, was also detected in controls and was confirmed to have no significant association with the risk for AD; Ile80Val was not detected in any normal controls, suggesting that the CHCHD2 gene may be associated with AD in the Chinese Han population.
Two missense variants, 5C>T (Pro2Leu) and 238A>G (Ile80Val), were identified in five unrelated patients with AD while no mutations were observed in patients with ALS or FTD.
However, we identified one rare variant, c.5C>T, a reported risk variant for sporadic PD in Japanese populations, and examined the frequency of three common variants.
Though the frequency of Pro2Leu variant was two times higher in PDcompared to controls, the difference did not reach significance in genotypic distribution (P = 0.47) or allelic distribution (P = 0.47).