Low Serum Levels of ABCA1, an ATP-Binding Cassette Transporter, Are Predictive of Preeclampsia

Abstract

Preeclampsia is a pregnancy-specific disorder characterized by hypertension and proteinuria, but the exact cause of preeclamptic hypertension remains unknown. ATP-binding cassette subfamily A member 1 (ABCA1) reverses cholesterol transport and eliminates excess cholesterol from tissues, whereas higher levels of cholesterol may lead to hypertension. Thus, ABCA1 affects the blood lipid profile. We have hypothesized that serum ABCA1 levels may influence the onset of hypertension and increase the risk of preeclampsia. To test this hypothesis, we measured serum ABCA1 levels in 50 normal pregnancies, 36 preeclamptic pregnancies, and 24 small-for-gestational-age (SGA) pregnancies during three trimesters. We also measured the concentrations of serum ABCA1 in non-pregnant women (n = 60), showing its normal ranges of 0.16 to 0.52 ng/ml. Importantly, the serum levels of ABCA1 were similar among non-pregnant women, normal pregnancies and SGA pregnancies. In contrast, the serum ABCA1 levels were significantly lower in preeclamptic pregnancies (0.06 ± 0.03 ng/ml) than those in non-pregnant women, and normal and SGA pregnancies (P < 0.05). Low serum ABCA1 levels were associated with the increases in the concentrations of blood lipid (low density lipoprotein cholesterol, total cholesterol and triglycerides) and with the decrease in the concentration of high-density lipoprotein cholesterol (P < 0.01), all of which may contribute to the onset of hypertension and eventually preeclampsia. Moreover, the preeclamptic pregnancy was diagnosed with high sensitivity from the nulliparous pregnancies if the cutoff value for serum ABCA1 was 0.06 ng/ml. Thus, low serum levels of ABCA1 are predictive of preeclampsia.

The impact of ATP-binding cassette transporters on metabolic diseases

“…In addition, ABC transporters are negatively correlated with fasting blood glucose, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and triacylglycerol levels [ 12 ]. Since abnormal lipid metabolism is associated with the pathogenesis of metabolic diseases, ABC transporters participate in the inhibition of metabolic diseases, including AS, hypoalphalipoproteinemia (HA), coronary artery disease (CAD) and TD [ 13 , 14 ].…”

Maternal cardiovascular-related single nucleotide polymorphisms, genes, and pathways associated with early-onset preeclampsia

“…In addition, while a history of preeclampsia is a well-established risk factor for future cardiovascular disease [15, 16], there is little information on genes common to both conditions. Some findings associated with preeclampsia in this study, such as MTHFR [17–19] and RGS5 [20] have been previously associated with preeclampsia, while maternal serum levels of TGFB2 [21] and ABCA1 [22] are altered in preeclampsia as well. While some effort has been undertaken to identify genetic associations between preeclampsia and cardiovascular disease, including PITX2 and chromosome locus 2q22, these studies were limited and used a candidate gene approach [23–25], as compared to our study which used a more global approach and studied under-represented populations such as the Native Hawaiians.…”

Common gene polymorphism in ATP‐binding cassette transporter A1 and coronary artery disease: A genetic association study and a structural analysis

“…Every variation in ABCA1 gene like polymorphic variants may result in malfunction of this protein 13 . ABCA1 gene has numerous variants in which the most common variant is the rs2230806 (c.1051 G > A; p.R219K) single‐nucleotide polymorphism (SNP) 14 . This variant is located on exon 7 of the gene and includes lysine amino acid substitution instead of arginine with derived c.1051GG, c.1051AG, and c.1051AA polymorphisms 9,15 .…”