Risk of obstetric cholestasis in sisters of index patients

Abstract

The aim of the present study was to evaluate the rate of intrahepatic cholestasis of pregnancy in first-degree relatives of index patients. Index patients (n=65) with singleton pregnancies complicated by intrahepatic cholestasis were identified among the women (n=11 984) who gave birth at Kuopio University Hospital in 1994-1998. The pregnancy histories of relatives of 56 index patients were reviewed and the rate of cholestasis in first-degree relatives was compared with that in the general obstetric population. Obstetric cholestasis was experienced by 9% of the parous sisters and 11% of the mothers of the index patients. The risk per delivery was 6% in the first-degree relatives. The rate in the general obstetric population was 0.54%. The odds ratios and 95% confidence intervals were 12.6 (5.6-28.1) for the sisters and 12.2 (6.2-24.2) for the mothers. Obstetric cholestasis clusters within some families and is under strong genetic influence, although the precise genetic pattern remains obscure. The sisters of index patients are at an increased risk of the disorder and may benefit from close obstetric care.

Reduced Antidiabetic Effect of Metformin and Down-regulation of Hepatic Oct1 in Rats with Ethynylestradiol-Induced Cholestasis

“…Estrogen has long been known to cause intrahepatic cholestasis in susceptible women during pregnancy (0.5-1.8% of pregnant women suffer from intrahepatic cholestasis, (13)(14)(15), after the administration of oral contraceptives, or during postmenopausal hormone replacement therapy (16). Experimental intrahepatic cholestasis induced by 17α-ethynylestradiol (EE) is a widely used in vivo animal model used to examine the molecular mechanisms involved in estrogen-induced cholestasis (17).…”

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

“…The ancestors of each patient and their birthplaces were traced back three generations to make sure that they were unrelated. 17 Hypertensive complications of pregnancy were classified as advocated by the US National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. 18 Preeclampsia was defined as the development of hypertension (4140/90 mmHg) and new-onset proteinuria (4300 mg of urinary protein in 24 h) in women with no proteinuria at baseline.…”

“…16 A familial tendency in obstetric cholestasis has been documented, suggesting that genetic factors contribute to its development. 17 On the basis of the reported linkage between preeclampsia and this chromosomal region, we have carried out population-based association mapping to document that this linkage is present across populations. Another aim was to clarify whether or not preeclampsia and obstetric cholestasis share a common risk locus.…”

Intrahepatic Cholestasis of Pregnancy and Cancer: A Cohort Study

“…Environmental factors may also have a role in the pathogenesis of the disorder [12]. In addition, a positive family history [13] and twin pregnancies raise the risk of ICP [14].…”