ABCA1 is expressed from β cells of the pancreas, and controls transcription network of various drugs, and proteins (6). However glucose upregulates in vivo ABCA1 expression from leukocytes, while insulin suppresses in vitro ABCA1 expression. (7, 8). Various studies have demonstrated that inactivation of ABCA1 in pancreatic β cells induces intracellular accumulation of cholesterol which progressively impairs insulin secretion leading to impaired glucose tolerance (9–11). Individuals with RR homozygous genotype carrying R219K polymorphism of the the ABCA1 gene are more sensitive to insulin relative to those conveying K minor alleles (106). In our study different G1051A (R219K) gene polymorphisms of ABCA1 G2706A (V771M), and ABCA1 genes were analyzed in consideration of diverse genotypes, and statistically significant difference was not detected among AA, AG, and GG genotypes as for fasting insulin, 2. hour postprandial blood sugar, fasting blood sugar, and HOMA-IR levels. Daimon et al. demonstrated the role played by ABCA1 genotype in the pathophysiology of type 2 DM independent from the levels of HDL cholesterol (12). Besides relationship between ABCA-1 lower HDL levels, obesity, and metabolic syndrome have been also displayed (13–15). R230C variant of ABCA1 is associated with low HDL cholesterol, obesity, and metabolic syndrome in Mexican population. Statistically significantly higher incidence (24.6%) of R230C/C230C genotype has been detected in Type 2 diabetics (16).
However in our study, statistically significantly higher rates of metabolic syndrome were detected in ABCA1 gene G1051A polymorphisms in patients with GA (p = 0.001, OR: 5.816) or AA (p = 0.039, OR: 3.619) genotype relative to GG genotype. Rates of metabolic syndrome did not statistically significantly differ among patients carrying ABCA1 G2706A polymorphism regarding GG, GA, and AA genotypes [GA vs GG genotype GG (p = 0.321, OR: 0.364), AA vs GG genotype (p = 0.438, OR: 0.534)].
In a study performed on 2752 healthy, and 1276 hypertensive patients in Japan, the correlation between ABCA 1 gene-14 C—> T polymorphism, and hypertension prevalence was detected. In separate analyses on both systolic, and diastolic blood pressures, statistically significant results have been found (17).
In our study, any difference was not found between genotypes regarding G1051A polymorphism of ABCA1 gene of the patients participated in our study, However in individuals carrying AA genotype, ABCA-1 2706 gene polymorphism was associated with lower systolic blood pressures when compared with those having AG, and GG genotypes (p = 0.027).
ABCA1 expression stimulates transformation of 3T3-L1 preadipocytes into mature adipocytes (120). Disruption of this process can effect lipid levels, increase in the secretion of some cytokines (IL-6, and TNF), fluctuate levels of regulatory adipocytokines as adinopectin, and resistin subsequently leading to development of atherosclerosis which is an inflammatory process. This change involving ABCA1 gene may increase levels of the markers of inflammation, and atherosclerosis.
In our study we analyzed both ABCA1 G2706A, and ABCA G1051A (R219K) gene polymorphisms, and demonstrated lack of any statistically significant difference among genotypes, when levels of hs-CRP, fibrinogen, and homocysteine levels were compared in dyslipidemic patients having different genotypes.
These results might be obtained because of the impact of diverse ABCA1 gene polymorphisms in different ethnic groups on hypertension, metabolic syndrome, and chronic diseases as type 2 diabetes through pathways dependent or independent on HDL-cholesterol. In a study performed in American population, in individuals with AA genotype, ABCA 1 G1051A (R219K) polymorphism was found to be associated with moderately high HDL levels, and lower prevalence of coronary artery disease (18).
However in our study, statistical analysis was performed between ABCA1 G1051A (R219K) gene polymorphism, and HDL –cholesterol levels, and statistically significantly higher HDL-cholesterol levels were detected in patients with GG genotype, when compared with those having AA, and AG genotypes (p = 0.047). In a previous study performed in a different population (Jerome I. Rotter et al.) the correlation between ABCA1 G1051A polymorphism, and increased HDL-cholesterol levels was stated. The same researchers indicated moderate LDL-cholesterol decrease in ABCA1 G1051A gene polymorphism (19, 20). In our study a statistically significant correlation was not detected between ABCA1 G2706A gene polymorphism, and HDL cholesterol levels (p = 0.670). This inverse outcome between ABCA1 G1051A gene polymorphism, and HDL cholesterol may be related to ethnic differences.