Association Of The CMIP Rs2925979 SNP And Serum Lipid Levels In The Guangxi Jing And Han Population

Background:It is well-known that dyslipidemia such as a low concentration of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo) A1, and high level of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and ApoB is an established risk factor for cardiovascular disease. Dyslipidemia is believed to be caused by various environmental and genetic factors, and their interactions. In a previous genome-wide association study, the c-Maf inducing protein gene (CMIP) rs2925979 single nucleotide polymorphism (SNP) has been associated with serum HDL-C levels in the individuals of European ancestry. But the reproducibility of this association has not been detected in the other populations. In addition, the genetic variation of this SNP has different magnitudes of effect in the different ethnicities. Thus, the purpose of the present study was to explore the association of the CMIP rs2925979 SNP and several environmental factors with serum lipid levels in the Guangxi Jing and Han populations.Methods:A cross-sectional study of dyslipidemia in the Jing and local Han populations was conducted by stratified (sex and age) randomized sampling at Jiangping town, Dongxing, Guangxi, China. This study included 552 unrelated subjects of Jing nationality comprising 226 males (40.9%) and 326 females (59.1%) and 632 unrelated participants of Han nationality including 269 men (42.6%) and 363 women (57.4%). They were randomly selected from our previous stratified randomized samples. The age of the Jing subjects ranged from 30 to 88 years, with an average age of 57.25±13.34 years, and the age of the Han participants ranged from 27 to 92 years, with an average age of 57.96± 13.07 years. The survey was carried out using internationally standardized methods. Information on demographics, socioeconomic status, and lifestyle factors was collected with standardized questionnaires. Several parameters such as height, weight, waist circumference, blood pressure, and serum lipid levels were measured, and body mass index (BMI, kg/m2) was calculated. Genomic deoxyribonucleic acid was isolated from peripheral blood leukocytes using the phenol-chloroform method. Genotyping of the CMIP rs2925979 SNP was performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), and then the genotypes were confirmed by direct sequencing.Results:Serum TC and TG levels were higher in Jing than in Han (P< 0.01). The frequencies of A and G alleles were 43.4% and 56.6% in Jing; and 42.4% and 57.6% in Han (P> 0.05); respectively. The frequencies of AA, AG and GG genotypes were 18.8%,49.1% and 32.1% in Jing, and 18.7%,47.4% and 33.9% in Han (P> 0.05); respectively. The genotypic distribution of the CMIP rs2925979 SNP was followed by the Hardy-Weinberg equilibrium. The AA, AG and GG genotypic frequencies of the SNP in Han but not in Jing were different between males and females (18.9%,52.8% and 28.3% vs.18.5%, 43.4% and 38.0%; respectively, P=0.028). Serum HDL-C levels in the Jing population were different among the genotypes (P=0.048), the G allele carriers had higher HDL-C levels than the G allele non-carriers. Serum TC levels in the Han population were different among the genotypes (P=0.007), the G allele carriers had lower TC levels than the G allele non-carriers. Subgroup analyses according to sex showed that serum TC levels in Han females were different among the genotypes (P= 0.032), the G allele carriers had lower TC levels than the G allele non-carriers. Multivariate linear regression analyses revealed that serum HDL-C and ApoB levels in the combined population of Jing and Han, and serum HDL-C levels and the ApoA1/ApoB ratio in Jing were correlated with genotypes (P< 0.05 for all). We also showed that serum lipid phenotypes were correlated with several environmental factors such as sex, age, height, weight, BMI, cigarette smoking, alcohol consumption, blood glucose, and blood pressure in the Jing and Han populations, or in males and females of the both ethnic groups (P< 0.05-0.001).Conclusions:The results of the present study show that the association of the CMIP rs2925979 SNP and serum lipid parameters is different between the Jing and Han populations, and between males and females of the both ethnic groups. These findings suggest that there may be an ethnic- and/or sex-specific association of the CMP rs2925979 SNP and serum lipid levels in our study populations.