Microsatellite marker association at chromosome region 2p13 in Finnish patients with preeclampsia and obstetric cholestasis suggests a common risk locus

Abstract

The pathophysiology of preeclampsia is incompletely understood, but the familial nature of the disease has long been recognized. Recent genome-scan studies have indicated linkage at the p23 region of chromosome 2. We have previously reported microsatellite marker association at chromosome region 2p13 in patients with obstetric cholestasis. We conducted population-based association screening with microsatellite markers to find potential preeclampsia-associated loci on chromosome region 2p13-p12 and to test whether preeclampsia and obstetric cholestasis share a single risk locus. The study was carried out among 115 unrelated control women, 133 preeclamptic women and 57 cholestatic women. Screening with microsatellite markers at the 2p13-p12 region revealed that the marker D2S286 was significantly associated with obstetric cholestasis in the overall association analysis (P ¼ 0.03), while it revealed only borderline association with preeclampsia (P ¼ 0.08). However, single allele association analysis indicated that both preeclampsia and obstetric cholestasis showed a statistically significant association with a common allele (P o 0.05), which was overrepresented in both the obstetric cholestasis (0.42) and preeclamptic (0.37) groups when compared with the control group (0.28). In conclusion, These findings suggest a possible genetic link between chromosome region 2p13-p12, preeclampsia and obstetric cholestasis. More specifically, these data suggest that there may be a common risk locus associated with both obstetric complications located in the vicinity of the 2p13-p12 association region.

Gamma 2 Actin Gene (Enteric Type) Polymorphism Is Not Associated with Obstetric Cholestasis or Preeclampsia

“…The LCHAD gene is located on 2p23 [16] . We have previously reported the obstetric cholestasis susceptibility locus on 2p13 [17] and more specifically our data suggest that there may be a common risk locus associated with both obstetric cholestasis and preeclampsia located at chromosome region 2p12-p13 [18] . On the basis of the reported connection between chromosome 2, specifically 2p12-p13, and both obstetric complications we decided to search for a candidate gene that may be relevant to both obstetric cholestasis and preeclampsia.…”

“…The ACTG2 gene locates on chromosome region 2p13.1 [19] , which has previously been reported to be connected to both obstetric cholestasis and preeclampsia [18] . Furthermore, actin genes may be candidate genes especially for pathogenesis of obstetric cholestasis [22] .…”

Genetics of preeclampsia: paradigm shifts

“…Within a large region in both chromosomes, shared features include the presence and similar line-up of paralogous genes (EGR2-CTNNA3-HK1-TACR2), genes predicted to be imprinted (LOXL3, DOK1, HK2, TACR1) and other features (FRA10D, FRA2E) ( Table 3) (Luedi et al 2005). The 2p13 locus previously found to segregate with two large Icelandic families has now been conWrmed to be associated with the Finnish populations as well (Arngrimsson et al 1999;Laasanen et al 2003). Ongoing searches for the 2p13 gene are likely to be successful if these similarities are taken into account, i.e.…”

“…This number is now clearly within reach for preeclampsia. Combination of the initiatives as the Dutch Preeclampsia study (150 aVected sibpair families selected from 3,000 patients), the British Genetics of Pre-Eclampsia (GOPEC) consortium (627 index pregnancies), and the Norwegian HUNT cohort (1138 preeclamptic women) complemented with the cohorts from Australia/New Zealand (34 pedigrees), Finland (15 families, 350 index pregnancies) and other countries provide adequate size and therefore power to provide precise genetic risks with narrow conWdence intervals (The GOPEC consortium 2005; Lachmeijer et al 2001;Arngrimsson et al 1999;Moses et al 2000;Laasanen et al 2003;Laivuori et al 2003;Moses et al 2006;Holmen et al 2003).…”

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

“…Este estudio incluyó 115 mujeres controles, 133 preeclámpticas y 57 mujeres colestásicas. El análisis de asociación alélica indicó que la preeclampsia y la colestasis obstétrica mostraron una asociación estadísticamente significativa con un alelo común del marcador D2S286, el cual estaba más frecuentemente en la colestasis intrahepática (0,42) y en la preeclampsia (0,37), cuando se compararon con el grupo control (0,28; p<0,05) (119). Estos hallazgos sugieren una posible relación genética entre la región 2p13-p12, la preeclampsia y la colestasis, indicando que podría contener un locus de riesgo común asociado con estas complicaciones obstétricas.…”