Our study validate the important role for CAD as the most frequent cause of mortality across the world according to data obtained from the World Health Organization (WHO) [13]. Causes of such unfortunate disease may be due to the complex interplay between genetic risk factors and environmental exposures that occur at critical times in development. Several epidemiological studies have shown that apolipoprotein A1/C3/A4/A5 gene cluster is found to be one of the factors that could cause premature CAD [14]. Among the gene cluster, APOA5 gene appears to affect TG levels [1]. Recently, several SNPs found in APOA5 cause an elevation in TG levels. A study has indicated that one of APOA5 SNPs, − 1131 T > C (rs2075291) variant, affects TG and HDL levels; therefore, increases the risk of developing cardiovascular diseases and diabetes [15]. Another study has shown that upon the transduction of AAV2/8-LacZ, AAV2/8-WT apoA-V and AAV2/8-G162C apoA-V, TG levels were lower in the WT mice when compared to both mutants [16]. In this study, we have described the relevance between the variant G162C (corresponding to c.553G > T) and TG levels in CAD patients who are on atorvastatin daily.
The incidence of diabetes in general population in Saudi Arabia is very high with up to 40% in some reports. It is possibly that the control group has many undiagnosed, untreated or borderline patients. On the other hand the CAD group most likely would be well treated patients and that is why there glucose levels are better.
Potential limitation of this study should be addressed. As the number of patients in each cohort is small to make conclusive results. Furthermore, there are differences between the control group and CAD group that may affect the results. Larger number of patients with TT allele is required to study in detail the effect of statin therapy on TG levels. Additionally, the duration and response to treatment was not studied in this report.
The frequency of c.553G > T allele in CAD patients was higher than normal subjects. Normally, the presence of T allele raises TG levels; yet, in patients carrying this allele and are on atorvastatin, it seems to lower TG levels. However, in a previous study, Ikejiri et al., stated that atorvastatin has no reduction effects on TG rich lipoproteins [12]. That conclusion is true regarding to the findings of TG levels in GG allele patients which showed no direct effects of atorvastatin on TG levels. In addition, there were no substantial differences in LDL between patients carrying T allele or the wildtype allele. Recent studies have revealed that APOA5 could affect cholesterol homeostasis and could cause hypertriglyceridemia [17]. Recent studies have revealed that APOA5 could affect cholesterol homeostasis and could cause hypertriglyceridemia [17] it is possible that statin therapy in these patients have more effect on TG metabolism given its effect on cholesterol hemostasis. Further mechanistic studies needs to be done on these patients. Another study that included Chinese subjects has shown that in CAD patients and control groups, the wild type GG carriers have considerably lower TG levels in comparison to the T allele carriers [18]. Regarding to HDL levels in the study subjects, T allele patients who were on atorvastatin have lower HDL levels than the other T allele patient who was not taking atorvastatin, but all results were in the normal range. This has been proven earlier by another Chinese study that showed no significant associations between the presence of T allele and lipid parameters including LDL, TC, and HDL [19]. As expected, cholesterol levels in T allele patients on atorvastatin were normal and lower than the T allele patient who was not on atorvastatin. This result is due to the fact that the pharmacological effect of atorvastatin is to lower cholesterol levels in the plasma. Previous studies have confirmed that atorvastatin reduces both LDL and total cholesterol, and it decreases cholesterol levels in females more than males [20]. The clinical implications for TG and CAD is less well studied compared to LDL levels. There is some associations but not as important as LDL and cholesterol levels on CAD. Medications that lower TG such as fenofibrates failed to improve outcomes compared to statin therapy in patient with CAD. Thus fenofibrates is indicated only in patients with very high TG levels despite diet control.
Finally, both T allele and the wildtype allele patients who were taking atorvastatin along with aspirin showed the lowest TG levels when compared to patients who were not on aspirin and/ or atorvastatin. These findings suggest that aspirin has an effect on TG levels when is taking with cholesterol medications; yet, further studies are needed to determine if there is an effect depending on the presence or absence of T allele. A study that was done on mice has revealed that aspirin decreases the secretion of VLDL- TG from the liver which in turn reduces HFD- induced hypertriglyceridemia supporting our findings in this study [21].