Association Of The APOA1 And CYP26A1 Single Nucleotide Polymorphisms And Serum Lipid Traits In The Maonan And Han Populations

Background: Maonan nationality belongs to a mountain ethnic minority in China.Little is known about the association of apolipoprotein A1 gene(APOA1)rs964184 single nucleotide polymorphism(SNP)and serum lipid levels in this population.The cytochrome P450 protein plays an important role in the synthesis of cholesterol and other lipids.However,there is little research about the relationship between the rs2068888 SNP near the cytochrome P450 26A1 gene(CYP26A1)and serum lipid profiles in the Chinese Maonan and Han populations.The aim of this study was to detect the association of the APOA1 rs964184 and CYP26A1 rs2068888 SNPs and several environmental factors with serum lipid levels in the Chinese minority Maonan and local Han populations.Methods: A epidemiological study was conducted at the Huanjiang Maonan Autonomous County of Hechi City,Guangxi Zhuang Autonomous Region,China.An experimental group including 867 unrelated participants of Maonan whose three generations of ancestors were Maonan nationality,and a control group including 820 unrelated subjects of local Han Chinese were randomly selected from our previous stratified(sex and age)randomized samples for the association of the APOA1 rs964184 SNP and serum lipid levels.Similarly,a total of 833 people from the Maonan and 701 local Han people were randomly selected according to gender and age stratifications for the association of the CYP26A1 rs2068888 SNP and serum lipid levels.Developing tables based on international standard cardiovascular epidemiological survey methods,and the demographic characteristics,socioeconomic status,and lifestyle were collected through standardized questionnaires,and inquiring and recording information about the history of cardiovascular disease medication,past medical history,family history,etc.Physical strength,weight,waist circumference and blood pressure were measured through physical examination.Serum lipid profiles were derived from the participants' elbow venous blood and the genomic DNA was extracted from the blood.Genotypes of the APOA1 rs964184 and CYP26A1 rs2068888 SNPs were identified by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)and agarose gel electrophoresis,and finally verified by directly sequencing.Results: As compared with local Han Chinese,the levels of systolic blood pressure,pulse pressure,serum triglyceride(TG)and apolipoprotein(Apo)A1 were higher in Maonan(P < 0.05-0.001),whereas the percentages of cigarette smoking,the levels of blood glucose and high-density lipoprotein cholesterol(HDL-C)were lower in Maonan than in Han(P < 0.001).There was no significant difference in the gender ratio,age structure,body height,weight,body mass index(BMI),waist circumference,the percentages of alcohol consumption,the levels of diastolic blood pressure,total cholesterol(TC),low-density lipoprotein(LDL-C),ApoB and the ratio of ApoA1/ApoB between the Maonan and Han(P > 0.05 for all).The three genotype frequencies(CC,CG and GG)of the APOA1 rs964184 SNP were 68.86%,29.18% and 1.96% in Maonan,respectively;and 63.78%,30.85% and 5.37% in Han population.The genotype distribution of the Maonan and Han populations was consistent with the Hardy-Weinberg equilibrium(HWE,P > 0.05).There were significant differences in genotype frequencies between the two ethnic groups(P < 0.001).Gender subgroup analysis showed that there was no significant difference in genotype and allele frequency between males and females in the Maonan and local Han ethnic groups(P > 0.05).Compared with Han,the G allele frequency of Maonan was lower(16.55% vs.20.79%,P < 0.05).The G allele carriers in the Maonan population had lower serum HDL-C levels than the G allele non-carriers(P < 0.05);the G allele carriers in the Han population had higher serum TG levels than the G allele non-carriers(P < 0.05).Subgroup analysis showed that the G allele carriers in Maonan males and females had lower serum HDL-C levels than the G allele non-carriers(P < 0.05 for each);the G allele carriers had lower serum ApoA1 levels and the ApoA1/ApoB ratio than the G allele non-carriers in the Han males(P < 0.05 for each)but not in the Han females(P > 0.05 for all).The correlations between serum HDL-C levels,ApoA1 levels and APOA1 rs964184 SNP genotypes were found by multiple linear regression analysis(P < 0.05).Similarly,serum HDL-C levels in the Maonan and TG levels in Han populations were associated with the genotype of APOA1 rs964184 SNP(P < 0.05 for each).Subgroup analysis showed that serum HDL-C levels in Maonan males was associated with genotypes(P < 0.05);serum ApoA1 levels and the ApoA1/ApoB ratio in Han males,and serum TG in Han females were all associated with genotypes(P < 0.05 for all).In addition,serum lipid parameters were also associated with age,gender,BMI,blood pressure(systolic and diastolic blood pressure),waist circumference,pulse pressure,fasting blood glucose,cigarette smoking and alcohol consumption in both ethnic groups,respectively(P < 0.05-0.001).Similarly,the genotypic and allelic frequencies of the CYP26A1 rs2068888 SNP were significantly different between the Maonan and Han.The frequencies of AA,AG and GG genotypes were 75.51%,23.41% and 1.08% in the Maonan population,and 64.62%,33.10% and 2.28% in the Han population(P < 0.001).The frequency of the G allele was 12.78% in Maonan and 18.83% in Han(P < 0.001).The level of serum TC was lower in Maonan than in Han.The G allele carriers had higher serum TC level in Maonan than the G allele non-carriers.Subgroup analyses indicated that the G allele carriers had lower serum TC level in Maonan females.Serum lipid parameters in the two ethnic groups were also associated with several environmental factors.Conclusions: The present study reveals that there may be a racial/ethnicand/or gender-specific association between the APOA1 rs964184 and CYP26A1 rs2068888 SNPs and serum lipid traits in our study populations.