Mutations in the lysyl oxidase gene are not associated with amyotrophic lateral sclerosis

BACKGROUND: There is an urgent need to identify genes involved in familial ALS (FALS), as mutations in the CuZn superoxide dismutase (SOD1) gene can a ccount for 20% of FALS cases. The mechanisms by which the many mutations in the SOD1 gene lead to motoneuron degeneration are unknown, although curren t experimental evidence supports a toxic gain of function, possibly through copper-induced cytotoxicity. Copper is an integral component of a number o f enzymes as well as SOD1. Since abnormalities in connective tissue cross-l inking have been reported in ALS patients, an enzyme of possible relevance is lysyl oxidase (LOX), a copper-containing enzyme which catalyses the cros slinking of collagens and elastin. The aim of this study was to investigate the hypothesis that allelic variants or mutants of LOX gene result in alte red function of LOX in AILS patients. METHODS: The coding regions of the LOX gene were screened for polymorphism and mutations in a cohort of sporadic and familial ALS patients. RESULTS: A novel polymorphism, Pro159Gln, was identified in eight individua ls with sporadic ALS (5.0%) and five controls (3.6%). The previously identi fied Arg158Gln polymorphism was also detected in ALS patients and controls. These polymorphisms were genotyped in 192 ALS patients, including 31 unrel ated familial cases and 138 controls, and no association was found between any of these polymorphisms and amyotrophic lateral sclerosis or its phenoty pe. CONCLUSION: Mutations in the LOX gene are unlikely to be directly causative of ALS.