Role Of Long Chain-3-hydroxyacylCoA Dehydrogenase Enzymes And The Mutations Of Its Encoding Gene Mutations In The Pathogenesis Of Acute Fatty Liver Of Pregnancy

ObjectiveAcute fatty liver of pregnancy (AFLP) is a rare condition that is almost always occurs in the third trimesters, and with the mortality of18%and23%in mother and fetus, respectively. The mechanism of AFLP remains unclear. Researches shed some light on possible relationship between AFLP and the defect of key enzyme in the procedure of fatty acid oxidation. LCHAD is one of three enzymatic activities in mitochondrial trifunctional protein (MTP), which catalyzes steps2to4of the long chain fatty acid β-oxidation spiral. The G1528C mutation and C1132T mutation causes isolated LCHAD deficiency which may inactivate LCHAD directly within the catalytic domain, and hence preserves the other MTP enzyme activities, then causes AFLP. The study of mechanism of AFLP is rare in China. In our study, we intended to research whether AFLP patients with Han nationality in Chinese have the common mutation in LCHAD, the expression of LCHAD in placentas, in order to explore the mechanism of AFLP.Methods1.12cases of cord blood samples, peripheral blood; from women and their infants were taken in pregnant women with Han nationality in Chinese. PCR-RFLP analysis was conducted for detection of G1528C mutation and C1132T.2. Placenta tissue were sampling from AFLP patients and normal pregnant women, the expression of LCHAD in placentas was analyzed using immunohistochemistry3. Expression of LCHAD in placentas from AFLP patients and normal pregnant women were observed by western blot.Results1. No G1528C and C1132T mutations in LCHAD gene were found in these study subjects.2. Protein of LCHAD was expressed in placenta of these two groups. Trophoblast cells contained brown granules, with the majority in the cytoplasm and the minority in the nucleus and core cells of the villi.3. Comparing with normal pregnant women, the expression of LCHAD protein was stronger in placentas from AFLP group.Conclusion1. G1528C and C1132T are probably not the common prevalent mutation in MTP gene in Chinese people. Different prevalent mutation between Chinese and Western white people needs further study.2. LCHAD protein expresses in placentas from the two groups, which is also the key enzyme in fatty acids oxidation. This suggests that FAO acts as a significant metabolic fuel and energy source for placenta formation and fetus development.3. The expressive quantity of LCHAD was with no abnormal which indicated the mechanism of AFLP maybe associated with the activity of LCHAD, the reason needs further study.