Abstract
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.
Highlights
Alkaline phosphatases (ALPs) catalyze the hydrolysis of organic phosphate esters in an alkaline environment and are highly expressed in liver, bone, intestine and placenta.1 In healthy subjects, serum alkaline phosphatase (ALP) is mainly derived from the liver, bone, kidney and partially from the intestine
We explored loci associated with serum ALP levels in a healthy Japanese population and identified an single-nucleotide polymorphisms (SNPs) in the fucosyltransferase 1 (FUT1) gene as a new marker associated with ALP levels
Gene–gene interaction analysis We evaluated the effects of the interaction between rs2071699 in the FUT1 gene and rs550057 in the ABO gene on the serum ALP level
Summary
Alkaline phosphatases (ALPs) catalyze the hydrolysis of organic phosphate esters in an alkaline environment and are highly expressed in liver, bone, intestine and placenta. In healthy subjects, serum ALP is mainly derived from the liver, bone, kidney and partially from the intestine. As opposed to non-secretors, secretors express the ABO antigen in their saliva, and intestinal ALP levels measured in the serum are higher in secretors than in non-secretors. Differences in serum ALP levels are present among the ABO blood serotypes; for example, the serum ALP level is higher in individuals with the ABO blood serotype B or O than in those with serotype A or AB. This difference occurs because blood type A erythrocytes bind almost all intestinal ALP in the serum, whereas blood type B or O erythrocytes bind a lower proportion of serum ALP.. This difference occurs because blood type A erythrocytes bind almost all intestinal ALP in the serum, whereas blood type B or O erythrocytes bind a lower proportion of serum ALP. The ABO blood serotype and secretor phenotype are determined by variants in the ABO blood (ABO) gene and the fucosyltransferase-2 (FUT2) gene, respectively.
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