Human GSTZ1 ELISA Matched Antibody Pair

Background A high level of succinylacetone (SA) in blood is a sensitive, specific newborn screening marker for hepatorenal tyrosinemia type 1 (HT1, MIM 276700) caused by deficiency of fumarylacetoacetate hydrolase (FAH). Newborns with HT1 are usually clinically asymptomatic but show liver dysfunction with coagulation abnormalities (prolonged prothrombin time and/or high international normalised ratio). Early treatment with nitisinone (NTBC) plus dietary restriction of tyrosine and phenylalanine prevents the complications of severe liver disease and neurological crises. Methods and results Six newborns referred for hypersuccinylacetonaemia but who had normal coagulation testing on initial evaluation had sequence variants in the GSTZ1 gene, encoding maleylacetoacetate isomerase (MAAI), the enzyme preceding FAH in tyrosine degradation. Initial plasma SA levels ranged from 233 to 1282 nmol/L, greater than normal (< 24 nmol/L) but less than the initial values of patients with HT1 (16 944-74 377 nmol/L, n= 15). Four individuals were homozygous for c.449C>T (p.Ala150Val). One was compound heterozygous for c.259C>T (p.Arg87Ter) and an intronic sequence variant. In one, a single heterozygous GSTZ1 sequence variant was identified, c.295G>A (p. Val99Met). Bacterial expression of p.Ala150Val and p.Val99Met revealed low MAAI activity. The six individuals with mild hypersuccinylacetonaemia (MHSA) were not treated with diet or nitisinone. Their clinical course has been normal for up to 13 years. Conclusions MHSA can be caused by sequence variants in GSTZ1. Such individuals have thus far remained asymptomatic despite receiving no specific treatment.

Preeclampsia (PE) is a complex disorder affected by genetic and environmental factors. Although the exact genes involved in development of PE are still not fully discovered, an important role for oxidative stress in its pathogenesis is accepted. In the present study, the association between the functional genetic polymorphisms in codons 32, 42 and nucleotide -1002 of glutathione S-transferases Z1 (GSTZ1) and susceptibility to PE was investigated. The present case-control study was performed on 151 preeclapmtic patients, and a total of 200 normal pregnant women, as a control group. The healthy control group was frequency matched with the age of the preeclamptic patients. Control subjects had no history of previous pregnancies with PE. Genotypes were determined by PCR-RFLP assay. There was no significant association between G-1002A and Glu32Lys polymorphisms of GSTZ1 with PE risk. The variant allele of Gly42Arg polymorphism decreased the risk of PE (OR = 0.24, 95 % CI 0.08-0.73, P = 0.012). The haplotype of "-1002A, 32Lys, 42Arg" (having three variant alleles) versus to the other haplotypes significantly decreased among PE patients compared to the control group (5.0 vs. 0.9 percent among control and PE patient groups, respectively; chi(2) = 9.328, df = 1, P = 0.002). The present results indicate that the haplotype of "-1002A, 32Lys, 42Arg" (containing three variant alleles) of GSTZ1 have protective effect compared to the other haplotypes.