Twin mothers, pregnancy hypertension and pre‐eclampsia

Abstract

Objective To estimate the maternal genetic contribution to the hypertensive diseases of pregnancy.Design A cohort study of female twins with information on hypertensive diseases of pregnancy obtained by questionnaire screening, and verification of diagnosis from hospital or general practitioner records.Setting A volunteer twin registry in the UK with recruitment through the media without reference to pregnancies or disease status.Population Adult female, same-sex twin pairs who completed a pregnancy history questionnaire and consented to record inspection.Main outcome measure Self-reported and hospital-validated diagnosis of non-proteinuric pregnancy hypertension and of pregnancy hypertension with proteinuria (pre-eclampsia).Results Self-reported pre-eclampsia had a heritability of 0.221 and non-proteinuric hypertension of 0.198. However, none of the pairs who were self-reported as concordant for pre-eclampsia were confirmed from hospital records. Using hospital records, the heritability of pre-eclampsia was 0 and 0.375 for non-proteinuric hypertension. Using a model treating pre-eclampsia as a separate disease from non-proteinuric hypertension, and assuming that the next pair identified was both monozygotic and concordant for pre-eclampsia, the estimated heritability of pre-eclampsia remained 0 (95% CI 0-0-49). Using a threshold model in which non-proteinuric hypertension is treated as a mild form of pre-eclampsia, heritability is estimated at 0.247 (95% CI 0.234454). ConclusionNeither non-proteinuric hypertension nor pre-eclampsia are inherited in simple Mendelian fashion. The genetic contribution to multi-factorial inheritance is smaller than hitherto believed.

The combination of ApoCIII, hepatic lipase and hormono sensitive lipase gene polymorphisms suggests an association with susceptibility to gestational hypertension

“…A number of studies have described a strong familial trend to developing HDP Chesley et al 1968;Chesley and Cooper 1986;Salonen Ros et al 2000), and recently a heritability estimate of 0.47 was observed for HDP in a large sample of over 2,000 twin pairs of women, indicating that HDP, both with proteinuria (PE) and without proteinuria (GH), is highly heritable (Salonen Ros et al 2000). Published data suggest a significant genetic component to HDP, which may include fetal and environmental factors (Broughton Pipkin 2001;Chesley and Cooper 1986;Cooper 1993;GOPEC Consortium 2005;Roberts and Cooper 2001;Salonen Ros et al 2000; Thornton and Macdonald 1999). Finally, it is still debated whether PE and GH represent different manifestations of the same entity or rather distinct pathogenic disorders (Brown et al 2001;Fisher et al 1981;Seely and Solomon 2003;Vatten and Skjaerven 2004).…”

“…There is evidence suggesting that HDP are multifactorial (Roberts and Cooper 2001;Talosi et al 2000; Thornton and Macdonald 1999), but the etiology and mechanisms causing PE and GH are still undefined. Current pathophysiological hypotheses imply inade-quate trophoblastic invasion, oxidative stress, endothelial dysfunction, inappropriate maternal immunological response and genetic susceptibility (Dekker and Sibai 1998;Roberts and Cooper 2001;Sibai et al 2005;Solomon and Seely 2001;Talosi et al 2000).…”

Investigation of the association between matrix metalloproteinase-9 genetic polymorphisms and development of pre-eclampsia in Chinese pregnant women

“…A previous study reported familial aggregation of pre-eclampsia, which suggests that genetic factors contribute to the pathogenesis of this disease (Morgan and Ward, 1999). Genetic factors account for 25 to 55% of the risk of developing pre-eclampsia (Thornton and Macdonald, 1999;Salonen Ros et al, 2000).…”

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

“…Además, esto se demuestra por las altas tasas de concordancia entre gemelas monocigóticas, comparadas con las dicigóticas (11)(12)(13). Sin embargo, el hecho de que también se hayan observado gemelas discordantes sugiere que el fenotipo fetal, al igual que los factores ambientales, pueden ser importantes en la susceptibilidad a la preeclampsia (14,15).…”