ATP-binding cassette transporter A1 gene polymorphisms and serum lipid levels in young Greek nurses

Abstract

ObjectiveThe ATP-binding cassette transporter A1 (ABCA1) is essential protein involved in lipid metabolism. The present study was undertaken to detect the possible association of polymorphisms in the ABCA1 gene [rs2230806 (R219K) and rs2230808 (R1587K)] and lipid profile in Greek young nurses.MethodsThe study population consisted of 308 unrelated nurses who were genotyped and the ABCA1 polymorphisms were detected. Additionally, lipid profile [total cholesterol (TC), triglycerides (TGs), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and apolipoprotein (apo) A] was evaluated.ResultsThere was no difference in the genotypic and allelic frequencies of the R219K polymorphism according to lipid profile. The R1587K genotypes differed significantly according to TC, LDL-C and TGs concentration (p = 0.023, p = 0.014 and p = 0.047, respectively). Particularly, significant difference in TC, LDL-C and TGs concentration was detected between RK and RR genotypes (p = 0.006, p = 0.004, p = 0.014, respectively). Women with RK genotype compared to RR genotype had higher concentration of TGs (134.25 mg/dl vs 108.89 mg/dl, p = 0.014, respectively), total cholesterol (207.41 mg/dl vs 187.69 mg/dl, p = 0.006, respectively), and LDL-C (110.6 mg/dl vs 96.9 mg/dl, p = 0.004, respectively).ConclusionsThese findings suggest that the R1587K polymorphism of ABCA1 gene was associated with lipid profile of Greek nurses. Women with RK genotype had higher TGs, total and LDL-C concentration compared to RR genotype. These observations may be significant in assessing the risk of CAD since a 1% change in LDL-C is associated with a 1% change of cardiovascular events. Also, TGs concentration were documented to play a significant role in women. However, this needs to be confirmed by larger studies.

Maternal ABCA1 genotype is associated with severity of Smith–Lemli–Opitz syndrome and with viability of patients homozygous for null mutations

“…The rare allele of the common ABCA1 SNP p.Arg1587Lys in the mother was found to be associated with decreased plasma HDL cholesterol and higher plasma cholesterol in young women. 21 In our investigation, it was associated with a milder SLOS phenotype without an effect on cholesterol concentration in the SLOS patients, which indicates a mode of action other than direct influence on cholesterol concentration. 26 Interestingly, p.Arg1587 is located in the second extracellular domain, which interacts directly with ApoA-I.…”

“…18,19,[23][24][25][26] Some common variants in the ABCA1 gene, such as the amino-acid exchange p.Arg1587Lys (R1587K), are known to result in low HDL cholesterol concentrations in the plasma, especially in women, as well as in higher plasma cholesterol and LDL levels. 20,21 Higher risk for ischemic heart disease and coronary heart disease was postulated in persons carrying the KK genotype (homozygous for p.Lys1587). 22 As 70% of SLOS patients show anomalies of the palate, the methylene tetrahydrofolate reductase (MTHFR) was also postulated as a possible modifier candidate.…”

Gender specific association of ABCA1 gene R219K variant in coronary disease risk through interactions with serum triglyceride elevation in Turkish adults

“…The 219K allele frequency of 0.38 in the Turks sample lies between frequencies reported as 0.25 in white subjects and 0.46 in Asians subjects (12,(27)(28)(29).…”

Functional and Structural Impact of ATP-Binding Cassette Transporter A1 R219K and I883M Gene Polymorphisms in Obese Children and Adolescents

“…Homozygotes of the A allele of R219K were associated with increased LDL-C and TC and decreased HDL-c concentrations in Turkish population [54]. Similarly, young Greek women with the GG genotype of the same SNP exhibited lower TC and LDL-c levels compared with the GA genotype [22]. In obesity, the K allele of the R219K polymorphism was also associated with lower HDL-c levels than controls among overweight/ obese Thai males, with no difference in HDL-c concentrations among genotypes of I883M polymorphism [10].…”

“…This polymorphism is located at the N-terminal extracellular loop of the ABCA1 protein which mediates its interaction with apoA-1 [17][18][19]. Despite the high number of case-control studies conducted to investigate the functionality of R219K variant, the results have been inconclusive [10,[20][21][22]. Another missense polymorphism, I883M with nucleotide change A[G in exon 18 at position 3044 (rs4149313, replaced by rs2066714), has been reported as a milder phenotype with a significant reduction of HDL-cholesterol (HDL-c) and cholesterol efflux (approximately 70 % of wild-type) [23][24][25].…”