Revealing the role of glutathione S-transferase omega in age-at-onset of Alzheimer and Parkinson diseases

Abstract

We previously reported a linkage region on chromosome 10q for age-at-onset (AAO) of Alzheimer (AD) and Parkinson (PD) diseases. Glutathione S-transferase, omega-1 (GSTO1) and the adjacent gene GSTO2, located in this linkage region, were then reported to associate with AAO of AD and PD. To examine whether GSTO1 and GSTO2 (hereafter referred to as GSTO1h) are responsible for the linkage evidence, we identified 39 families in AD that lead to our previous linkage and association findings. The evidence of linkage and association was markedly diminished after removing these 39 families from the analyses, thus providing support that GSTO1h drives the original linkage results. The maximum average AAO delayed by GSTO1h SNP 7-1 (rs4825, A nucleotide) was 6.8 (+/-4.41) years for AD and 8.6(+/-5.71) for PD, respectively. This is comparable to the magnitude of AAO difference by APOE-4 in these same AD and PD families. These findings suggest the presence of genetic heterogeneity for GSTO1h's effect on AAO, and support GSTO1h's role in modifying AAO in these two disorders.

Figure 1

Comparison of the multipoint linkage results for AAO on chromosome 10 using the full linkage data set [9] (dot line), the same data set without the 39 families showing positive association and linkage information (solid line), and the same linkage data set without families with positive MK scores (93 families) (dash-dot line).

Figure 2

The distribution of AAO differences between the SNP 7-1 carriers and SNP 7-22 individuals in the overall AD data set, positive association subset, and the 39 families with strong association and linkage signals.