In the present study, we assessed the potential association between Hcy and apoAI levels in normal healthy people. HHcy subjects exhibited significantly lower HDL-C and apoAI levels than the control group. The plasma Hcy levels were negatively associated with HDL-C and apoAI levels after adjusting for age, BMI and TG. Multivariate regression analysis showed that the plasma Hcy level was an independent influencing factor for apoAI.

HHcy is often associated with essential hypertension [14]. Our previous studies showed that IGT patients with HHcy had a higher prevalence of essential hypertension [11]. HHcy increased blood pressure mediated through the disruption of the bioavailability of tetrahydrobiopterin and caused vascular endothelial dysfunction [14]. In the present study, we observed healthy participants without essential hypertension and found that Hcy was positively correlated with the SBP and DBP levels in the HHcy group. Subjects with a high-normal blood pressure exhibited decreased artery elastic function and endothelial dysfunction [15, 16]. Thus, HHcy may potentially enhance the levels of blood pressure even within the normal range, and elevated blood pressure is one factor that is likely to mediate cardiovascular disease in HHcy patients.

Our previous studies showed that Hcy contributes to insulin resistance by inducing endoplasmic reticulum stress, upregulating the expression of resistin, and interrupting the phosphorylation of insulin receptor tyrosine kinase [17]. In IGT patients, plasma Hcy levels are positively related to HOMA-IR [11]. Hypertensive patients with HHcy had significant insulin resistance compared to patients without HHcy [5]. However, in the present study, there was no correlation between Hcy and HOMA-IR not only in all of the participants but also in the HHcy subjects. Insulin resistance is associated with obesity, dyslipidemia and hypertension and other metabolic risk factors [18]. IGT and hypertensive patients had obvious metabolic disorders [19]; however, the present study investigated normal healthy people who did not have hypertension, diabetes and other overt metabolic diseases. Thus, it might suggest that HHcy had a synergistic promoting effect on insulin resistance with metabolic risk factors, but HHcy had a weaker effect by itself on insulin resistance compared to hypertension, diabetes and obesity.

HDL is a lipoprotein that is produced in the liver [9]. It has anti-atherogenic properties by transporting cholesterol from cells into peripheral tissues, reducing oxidative stress and suppressing inflammatory pathways [9]. ApoAI is a major functional component of HDL and is extensively involved in the cardiovascular protective effects of HDL [10]. Transgenic over-expression of apoAI mice exhibit elevated plasma HDL-C levels and reduced vascular lesions [20]. Low apoAI (HDL-C) levels are a risk factor for atherosclerosis [9, 21]. However, the underlying mechanism of low apoAI (HDL-C) levels still remains unknown. Some factors, including obesity and smoking, have been reported to reduce HDL-C and apoAI levels [22]. Recent studies have presented a correlation between Hcy and apoAI. Recent animal and in vitro cell studies have also demonstrated that Hcy suppresses hepatic apoAI expression via the peroxisome proliferator activated receptor α (PPARα) - apoAI pathway [12, 23, 24]. Moreover, Hcy could decrease the transcription of apoAI by stimulating nuclear factor κB (NF-κB) and apoAI regulatory protein-1 (ARP-1) [19, 25]. Decreased plasma and hepatic expression levels of apoAI have also been observed in animal models of HHcy [12, 26]. Data from population studies in IGT patients and male patients with coronary artery disease showed that Hcy levels are negatively correlated with apoAI levels [12]. In the present study, plasma Hcy levels were negatively associated with the HDL-C and apoAI levels in normal healthy people, and plasma Hcy levels were an independent influencing factor for apoAI levels. Thus, it might suggest that HHcy is involved in the development of low plasma levels of apoAI and HDL-C in healthy people, and the inhibition of apoAI synthesis is a subsequent mechanism through which Hcy is linked to atherosclerosis development in HHcy patients. However, inconsistently, a recent study showed that the plasma folate, but not Hcy, is associated with apoAI levels in a non-fortified population [27]. One possible explanation for this opposing result is that not all participants in that study were fasting at the time of blood sampling, and the levels of Hcy, folate and blood lipid may be influenced by eating [27]. Unfortunately, our study did not assess the serum folate levels of the participants. We will address this issue in our further research.

Our study has several limitations. The major limitation was that we did not assess the serum folates and MTHFR polymorphisms (677C > T and 1298A > C) which had been demonstrated as the determinant of the plasma Hcy levels. Additionally, as a cross-sectional study, it is hard to confirm causality. Further prospective or intervention researches are needed to evaluate the potential association between Hcy and apoAI levels.