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

In the present genome-wide association study of 2,994 Japanese subjects, rs2071699 (35C>T) in the fucosyltransferase 1 (FUT1) gene was identified as a marker associated with serum alkaline phosphatase (ALP) levels. This gene encodes α(1,2)-fucosyltransferase, which is responsible for the synthesis of H antigens. In a linear regression model incorporating genetic markers, rs550057 (C>T), which is located within an intron of the ABO blood group (ABO) locus, rs2071699 in FUT1 and a gene–gene interaction between these loci accounted for 12.4, 0.9 and 0.3% of the total variability in the serum ALP level, respectively. Further association analysis using imputed genotypes detected rs1047781 in FUT2. rs1047781 is well known in this association with serum ALP levels and showed a moderate linkage with rs2071699 in FUT1. An interaction analysis using rs1047781 in FUT2 also suggested that the interaction with rs550057 in ABO is significant and contributes to the interindividual variance of serum ALP levels as well as rs2071699 in the FUT1 gene. Thus, there is evidence of interactions between ABO and FUT1/FUT2 on serum ALP levels, regardless of the possibility that rs2071699 in FUT1 is a proxy of rs1047781 in FUT2 in the Japanese population.