Alkaline Phosphatase, Plasma Level Of, Quantitative Trait Locus 1

Other quantitative trait loci involved in the plasma level of alkaline phosphatase (see 171760) include ALPQTL2 (612367) on chromosome 1p36, ALPQTL3 (612368) on chromosome 6p22, and ALPQTL4 (612369) on chromosome 10q21.

Clinical Features

Wilson (1979) described a family in which 5 persons in 3 generations showed elevated serum alkaline phosphatase in the absence of disease. In 2 instances the apparently autosomal dominant trait was transmitted from father to son. The elevation of enzyme activity represented increased liver and bone isozymes.

McEvoy et al. (1981) reported a family with both parents and all of 7 children affected showing elevation of liver, bone, and intestinal isozymes. Ducobu and Dupont (1981) reported a family with 6 affected persons.

Siraganian et al. (1989) described a family in which both parents and all 4 children showed serum total alkaline phosphatase activity that was greater than the population mean; 2 of the 4 offspring had levels greater than 7 SDs above the mean. Monoclonal antibodies to 3 alkaline phosphatase isoenzymes, intestinal (ALPI; 171740), placental (ALPP; 171800), and tissue nonspecific (liver/bone/kidney; ALPL; 171760), demonstrated increased intestinal alkaline phosphatase levels (29 to 44% of total) in all family members and significantly elevated liver/bone/kidney activity in the 2 offspring. The mode of inheritance in this family is obscure. Complex regulation of the products of 2 different alkaline phosphatase genes is possible.

See also the reports by Parker and Ghishan (1980), Cirera Nogueras et al. (1982), and Kruse (1983).

Mapping

Yuan et al. (2008) performed a genomewide association study of plasma liver-enzyme levels in 3 populations (total n = 7,715) with replication in 3 additional cohorts (total n = 4,704). They identified a locus on chromosome 9q34.13 encompassing the ABO blood group genes (110300), with most significant linkage for rs657152 (p = 1.7 x 10(-30)). Yuan et al. (2008) noted that an association between ABO blood group and plasma alkaline phosphatase level had been reported by Whitman and Martin (1983).

Chambers et al. (2011) carried out a genomewide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma. The strongest association for ALP was at 9q34 with rs579459 with an effect of 8.8%, 95% CI 7.4-10.2, p = 2.6 x 10(-123). The gene of interest is in the area of ABO.