Interaction of genetic markers associated with serum alkaline phosphatase levels in the Japanese population.

Common genetic variants interact to affect expression of an enzyme associated with liver disease, bile duct problems and bone disorders. Tsutomu Fujiwara and colleagues from Otsuka Pharmaceutical in Osaka, Japan, analyzed close to 2.4 million letters of DNA in a cohort of 2,994 healthy individuals of Japanese ancestry. They also measured blood levels of alkaline phosphatase (ALP), an enzyme produced primarily in the liver and in bone. They found a previously unrecognized link between levels of ALP and versions of the FUT1 gene, which is involved in producing ABO blood group antigens. They also demonstrated interactions between FUT1 and other genes similarly implicated in both blood group type and ALP. These results suggest that doctors should consider these natural genetic variants and their interactions when establishing healthy levels of ALP in a clinical setting.