The etiology of intrahepatic cholestasis of pregnancy (ICP) involves various factors such as environmental factors, hormonal balance, and genetic components. The relation of the genetic factors lead to the various prevalence rates among different ethnic groups. It has been reported that the prevalence in Caucasians in Europe, United States, Canada, and Australia ranges from 0.1% to 1.5% [
1]. On the other hand, much fewer number of cases have been reported in Asian countries [
2]. Symptoms include itching, particularly of the palms and feet, and jaundice. Fetal consequences of ICP include spontaneous preterm labor, fetal distress, and intrauterine death due to increased levels of serum bile acids [
1‐
5]. Biochemical analysis shows a mild increase in transaminases, bilirubin, other biliary enzymes, and serum bile acids levels of >10 μmol/L [
6,
7]. In addition, the level of cytotoxic bile acids, such as chenodeoxycholic acid, increases 10-100 times higher than the normal level. Symptoms and serum abnormalities abate after delivery; however, recently, reviews have reported that ICP is also related to an increased risk of developing hepatobiliary diseases later in life [
8]. More recently, results of comprehensive analysis of genetic variation in ICP have been reported, and common variations around
ABCB4 and
ABCB11 encoding multidrug resistance protein 3 (MDR3) and bile salt export pump (BSEP), respectively, have been reported as key factors [
1,
6]. Similar results have been reported that
ABCB4[
9‐
13] and
ABCB11[
14] have significant relationships with the etiology of ICP. The combination of these mutations has been reported to be related to severe ICP. For example, the combination of homozygous polymorphisms in
ABCB11 at the complementary DNA position 1331 with a thymine replaced by a cytosine (1331 T > C, rs2287622), leading to an exchange from valine to alanine (V444A), and in
ABCB4 at position 959 in exon 9 with a cytosine replaced by a thymine (959 C > T), leading to an exchange of serine to phenylalanine (S320F), and some other synonymous SNPs are considered to be related to the etiology of severe type of ICP [
15]. Further analysis has shown that the association of 1331 T > C (rs2287622) was also driven by other SNP (rs3815676) [
1]. Therefore, these genetic variations may contribute to the difference of the occurrence in ethnic groups and further studies will clarify the more accurate contributions of each variation, since these SNPs have also been found in general population [
16‐
18]. Here, we report the first case of a Japanese woman diagnosed with ICP based on severe pruritis, increased levels of bile acid and hepatobiliary enzymes, and successfully treated with ursodeoxycholic acid (UDCA) preventing fetal death and clinical symptoms as well. The genetic sequence analysis showed a homozygous polymorphism in
ABCB11 at 1331 T > C leading to V444A that is often reported in the conditions [
1,
15]. Furthermore, another synonymous single-nucleotide polymorphism in
ABCB4 (504 C > T, rs1202283, N168N) was combined in our patient that have never been reported the association with this disease. Based on these results, we concluded our case as a first Japanese case of severe ICP with mutations in
ABCB11 and
ABCB4. Further study will help us to find and appropriately treat patients preventing fetal death and clinical symptoms.