A Genome Scan in Families from Australia and New Zealand Confirms the Presence of a Maternal Susceptibility Locus for Pre-Eclampsia, on Chromosome 2

Abstract

Epidemiological studies have shown that genetic factors contribute to the etiology of the common and serious pregnancy-specific disorder pre-eclampsia (PE)/eclampsia (E). Candidate-gene studies have provided evidence (albeit controversial) of linkage to several genes, including angiotensinogen on 1q42-43 and eNOS on 7q36. A recent medium-density genome scan in Icelandic families identified significant linkage to D2S286 (at 94.05 cM) on chromosome 2p12 and suggestive linkage to D2S321 (at 157.5 cM) on chromosome 2q23. In the present article, the authors report the results of a medium-density genome scan in 34 families, representing 121 affected women, from Australia and New Zealand. Multipoint nonparametric linkage analysis, using the GENEHUNTER-PLUS program, showed suggestive evidence of linkage to chromosome 2 (LOD=2.58), at 144.7 cM, between D2S112 and D2S151, and to chromosome 11q23-24, between D11S925 and D11S4151 (LOD=2.02 at 121.3 cM). Given the limited precision of estimates of the map location of disease-predisposing loci for complex traits, the present finding on chromosome 2 is consistent with the finding from the Icelandic study, and it may represent evidence of the same locus segregating in the population from Australia and New Zealand. The authors propose that the PE/E-linked locus on chromosome 2p should be designated the "PREG1" (pre-eclampsia, eclampsia gene 1) locus.

Placental expression profiling in preeclampsia: local overproduction of hemoglobin may drive pathological changes

“…Linked loci have been found on chromosomes 2 (2p13 (15,16) and 10 (10q22q22 (17)) but to date no specific genes in the linked loci have been implicated in causing the problem. However, changes in the expression of several genes in the placenta have been proposed to affect the development of PE.…”

A genome-wide scan for preeclampsia in the Netherlands

“…23 Evidence for a preeclampsia locus on chromosome 2 was confirmed by a similar genome-wide scan in 34 families from Australia and New Zealand from Moses et al who found suggestive evidence of linkage to chromosome 2q at 144.7 cM. 24 The current Dutch genome-wide scan was performed at the same laboratory as and in close collaboration with Arngrõ Âmsson and coworkers; 265 individuals from 67 Dutch families were genotyped at 293 microsatellite markers.…”

“…We re-analysed our data for families with only preeclampsia cases (preeclampsia families; n=38) and families with at least one sibling with HELLP-syndrome (HELLP families; n=34) separately, since in the previous scans 22,24 no HELLPsyndrome cases had been recruited. Figure 1 Results genome-wide scan in 67 Dutch families.…”

“…Other regions where both scans had nominal peaks were 2q, 13p and 18p. The most recent large genome-wide scan using Australian and New Zealand (NZ) families 24 had its highest peak on chromosome 2q (lod score=2.58 at 144.7 cM) with a broad basis overlapping the broad basis of the significant peak in the Icelandic scan on chromosome 2p (lod score 4.77 at 94.05 cM). The area harbouring the two peaks was designated the`PREG1' locus.…”

Genética de la preeclampsia: una aproximación a los estudios de ligamiento genético.

“…Al reevaluar las familias con HELLP, se encontró un LOD score en el cromosoma 12q que incrementó en las familias con HELLP y casi desapareció en las familias que no tenían el síndrome. Otro valor observado en un marcador en el cromosoma 11, en las familias con preeclampsia se traslapó con el segundo valor más alto en el estudio australiano (116). A pesar de la diversidad de resultados encontrados en este estudio en comparación con los estudios previos, los autores concluyeron que según este barrido genómico el síndrome HELLP podría tener una base genética diferente a la de la preeclampsia sin HELLP.…”