Variant that raises intrahepatic cholestasis risk is HBV protection
Epidemic in East, Southeast Asia 3,000 years ago may have led to ICP mutation
A genetic variant unique to East Asians increases the risk of intrahepatic cholestasis of pregnancy (ICP) by more than 16 times, but it likely became common in the region within the last 3,000 years because it confers protection against hepatitis B, a study finds.
“These findings are crucial for researchers studying pregnancy-related liver disorders and clinicians providing care to pregnant women, enabling more accurate screening, risk assessment, and targeted interventions for ICP,” the study’s researchers wrote.
The study, “Genetic study of intrahepatic cholestasis of pregnancy in Chinese women unveils East Asian etiology linked to historic HBV epidemic,” was published in the Journal of Hepatology.
After the middle stages of pregnancy, some women develop a form of cholestasis called ICP. In cholestasis, the flow of bile through the tubes that take it to the small intestine to help with digestion is slowed or stopped, causing it to build up in the liver and leak into the bloodstream.
The prevalence of ICP, that is, how common the disease is, varies from country to country. To better understand how these differences originated, the researchers screened the entire set of DNA of a large group of East Asians as part of a genome-wide association study to search for small variations that may be linked to ICP.
Based on data from 98,269 pregnancies in Chinese women, the researchers identified eight genetic regions linked to levels of bile acid, a main component of bile, and four linked to ICP. Among these, 10 were new.
A helpful mutation leads to increased ICP risk
A specific genetic variant in a small region of the genome, 14q24.1, was found to be unique to East Asians. This variant increased the total serum (blood) bile acid levels at fasting by 6.12 micromoles per liter and the risk of ICP by 16.56 times for each copy of it.
Compared with Europeans, East Asians had a much stronger genetic link to ICP, suggesting genetics may influence how common the disease is in different populations.
The variant at 14q24.1 may have helped protect against the hepatitis B virus (HBV), which causes hepatitis B, an infection of the liver. This genetic variant may have become more common around 3,000 years ago in East and Southeast Asia because it offered survival benefits during an epidemic.
“Our study suggests that a potential HBV epidemic in East and Southeast Asia around 3,000 years ago may have led to the positive selection of the ICP risk allele, resulting in its current prevalence in these regions,” the researchers wrote.
What was once helpful for fighting HBV now contributes to a higher risk of ICP, underscoring how diseases can be shaped by historical events and genetic changes in specific populations. Understanding these connections helps explain why certain diseases affect some populations more than others. For doctors, the study provides valuable information to improve ICP screening and care for East Asian women.
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