Polymorphism in the TOMM40 gene modifies the risk of developing sporadic inclusion body myositis and the age of onset of symptoms.

[inclusion body myositis]

A polyT repeat in an intronic polymorphism (rs 10524523 ) in the TOMM 40 gene , which encodes an outer mitochondrial membrane translocase involved in the transport of amyloid-β and other proteins into mitochondria , has been implicated in Alzheimer 's disease and APOE -TOMM 40 genotypes have been shown to modify disease risk and age at onset of symptoms . Because of the similarities between Alzheimer 's disease and sporadic inclusion body myositis (s-IBM ), and the importance of amyloid-β and mitochondrial changes in s-IBM , we investigated whether variation in poly-T repeat lengths in rs 10524523 also influence susceptibility and age at onset in a cohort of 90 Caucasian s-IBM patients (55 males ; age 69 .1 ± 9 .6 ). In carriers of APOE ε 3 /ε 3 or ε 3 /ε 4 , genotypes with a very long (VL ) poly-T repeat were under-represented in s-IBM compared to controls and were associated with a later age at symptom onset , suggesting that these genotypes may be protective . Our study is the first to suggest that polymorphisms in genes controlling mitochondrial function can influence susceptibility to s-IBM and have disease modifying effects . However , further studies in other s-IBM populations are needed to confirm these findings , as well as expression studies of different TOMM 40 alleles in muscle tissue .