The results of the present study show that the levels of TG, HDL-C, ApoA1, and the ratio of ApoA1 to ApoB were higher in drinkers than in non-drinkers, whereas the levels of TC, LDL-C and ApoB were lower in drinkers than in non-drinkers. The subjects with AA genotype of PCSK9 E670G had lower serum TC and LDL-C levels in drinkers than in non-drinkers. The interactions between PCSK9 E670G genotypes and alcohol consumption on serum TC and LDL-C levels were also detected by using a factorial design covariance analysis after controlling for potential confounders. These findings suggest that the effect of alcohol consumption on serum TC and LDL-C levels may depend on the PCSK9 E670G genotypes. To the best of our knowledge, the interaction between PCSK9 E670G SNP and alcohol consumption on serum lipid levels has not been previously explored.
In the present study, we showed that the frequencies of G allele and AG genotype of PCSK9 E670G SNP was 2.6% and 5.2% in non-drinkers, and 2.1% and 4.2% in drinkers (P
> 0.05 for each); respectively. There was no significant difference in the genotypic and allelic frequencies between males and females in both groups. Several previous studies showed that the minor-allele frequency (670G) was rare in whites but presented in approximately 24.8% of blacks 35,44
. The frequency of the G allele in patients selected from Universitätsklinikum Hamburg-Eppendorf Martinistrasse, Hamburg, Germany was 5% 37
which lies between that observed in the TexGen population, 4.4% and that reported for the Lipoprotein Coronary Atherosclerosis Study (LCAS), 7.4% by Chen et al. 36
in their original study. There was no statistical significant difference in the frequency of the G allele in patients with LDL-C below the 50th percentile for age and sex, those with LDL-C between the 50th and 95th percentiles, and those with LDL-C above the 95th percentile 37
. The 670G carrier in Chinese Taiwanese was identified less frequently in patients with CAD than in controls (9.9% vs. 11.9%), but the difference was not significant in a multivariable logistic regression analysis 39
. These results indicate that the prevalence of the G allele variation of PCSK9 E670G may have a racial/ethnic specificity.
The association of PCSK9 E670G SNP and serum lipid levels is still controversial. Chen et al. 36
showed that PCSK9 E670G was an important determinant of plasma LDL-C levels, accounting for 3.5% of its variability (F
= 14.6, P
< 0.001). Accordingly, LDL-C levels were higher in those with the GG, intermediate in those with the AG, and lowest in those with the AA genotypes. Plasma TC, ApoB, and lipoprotein (a) levels were also associated with the PCSK9 E670G SNP. Evans and Beil 37
found that the PCSK9 E670G SNP in a European population was associated with increased LDL-C in men but not in women. Norata et al. 38
also showed that the 670G carriers were associated with increased plasma TC, LDL-C, and ApoB levels in the general population. Contradictory to these previous results, Hsu et al. 39
showed a significantly lower level of LDL-C in 670G carriers in Chinese Taiwanese than in non-carriers among 614 unrelated controls. However, the association between the PCSK9 E670G SNP and plasma LDL-C levels or CAD risk was not confirmed in other studies 35, 42-44
. In the present study, we showed that the levels of LDL-C in non-drinkers were different between the two genotypes, the subjects with AA genotype had higher LDL-C levels than the subjects with AG genotype. The levels of TC in drinkers were different between the two genotypes, the subjects with AG genotype had higher TC levels than the subjects with AA genotypes. Multiple linear regression analysis showed that the levels of serum TC and LDL-C in non-drinkers were negatively correlated with the genotypes of PCSK9 E670G, whereas the levels of TC and TG in drinkers were positively associated with the genotypes of PCSK9 E670G. The reason for this discrepancy is most likely due to different gene-environmental interactions.
There are several potential limitations in the current study. First, we did not match drinkers and non-drinkers in terms of sex; therefore, the drinkers had a much higher proportion of males than did the non-drinkers. Second, the sample size of drinkers is a little small. In addition, the subject with GG genotype is not detected in both drinkers and non-drinkers. Third, the levels of body height, weight, and the percentages of subjects who smoked cigarettes were higher in drinkers than in non-drinkers, whereas the levels of mean age and diastolic blood pressure were lower in drinkers than in non-drinkers. Although sex, age, BMI, hypertension, and cigarette smoking have been adjusted for the statistical analysis, we could not completely eliminate the potential effects of these factors on serum lipid levels in both groups. Fourth, the use of questionnaire may not be a reliable measure for alcohol intake in our population because 90% of the wine drunk by the drinkers was corn wine, rice wine, and rum, in which the alcohol content is very low. Fifth, it is well known that serum lipid levels are modulated by multiple environmental and genetic factors, and their interactions. Although we have detected the interactions of PCSK9 E670G SNP and alcohol consumption on serum lipid levels in this study, there are still many unmeasured environmental and genetic factors and their interactions. Thus, the interactions of environment-environment, environment-gene, and gene-gene on serum lipid levels remain to be determined. Finally, the number of 670G allele carriers in our study populations is rather small, the findings in our current study should be confirmed in the other populations.