Association Of The KLF14rs4731702SNP And Serum Lipid Levels In The Guangxi Mulao Population

Background and objective: Genome-wide association studies are rapidlyunraveling the role of genetic factors in the pathogeneses of dyslipidemia.Findings from large scale studies suggested a strong linkage between the geneticvariants at the Krüppel-like factor14(KLF14) locus and serum lipid levels.KLF14is an intronless member of the KLF family located at chromosome7q32.The KLF14is shown to act as a master role in regulating the expression ofadipose genes that associated with key metabolic traits. The single nucleotidepolymorphism (SNP) of rs4731702~14kb upstream of KLF14has beenimplicated a highly-correlation with high-density lipoprotein cholesterol(HDL-C) and cardiovascular diseases. However, little is known about the exactimpact of this SNP on lipid metabolism. Mulao nationality is a relativelyconservative and isolated minority in China that retaining their regional and special customs. The engagements of Mulao nationality were intra-ethnic. Webelieved that some hereditary characteristics and genotypes of lipidmetabolism-related genes in this population might be different from those inHan Chinese. The objective of the present study was to detect the association ofthe rs4731702SNP and serum lipid levels in the Guangxi Mulao and Hanpopulations.Method: This study included727participants of Mulao and740participants of Han Chinese who were randomly selected from our previousstratified randomized samples. Epidemiological survey was carried out usinginternationally standardized methods. A standard questionnaire collecting theinformation on demographics, socioeconomic status, and lifestyle factors wasobtained from all the subjects. Anthropometric measurements were obtained bytrained personnel of health care centers including height, weight, waistcircumference and blood pressure. Biochemical parameters including totalcholesterol (TC), triglyceride (TG), HDL-C, low-density lipoprotein cholesterol(LDL-C), apolipoprotein (Apo) AI and ApoB were measured. The genomicDNA was obtained from peripheral lymphocytes using the phenol-chloroformmethod. Genotyping was carried out by polymerase chain reaction andrestriction fragment length polymorphism (PCR-RFLP). Six samples detected bythe PCR-RFLP were also confirmed by direct sequencing.Results: The levels of body mass index (BMI), diastolic blood pressure, and the ratio of ApoAI to ApoB were lower in Mulao than in Han (P <0.05-0.001), whereas the levels of body height, LDL-C, ApoB, and thepercentages of subjects who consumed alcohol were higher in Mulao than inHan (P <0.05-0.001). The frequencies of CC, CT and TT genotypes of theKLF14rs4731702SNP were44.5%,40.0%and15.5%in Mulao, and47.0%,39.2%and13.8%in Han; respectively. There was no significant difference ineither genotypic or allelic frequencies between Mulao and Han (P>0.05). Thegenotypic and allelic frequencies in Han were different between males andfemales (P <0.05). The T allele carriers had higher serum LDL-C and ApoAIlevels in Mulao, whereas lower high-density lipoprotein cholesterol (HDL-C)levels and the ratio of ApoAI to ApoB in Han (P <0.05) than the T allelenon-carriers. Subgroup analyses showed that the T allele carriers had higherHDL-C, LDL-C and ApoAI levels in Mulao males, and lower ApoAI levels andthe ratio of ApoAI to ApoB in Han males than the T allele non-carriers. Thesubjects with TT genotype in Han females also had higher TC, LDL-C, ApoAIand ApoB levels than the subjects with CT or CC genotype. Serum lipidparameters were also correlated with age, sex, BMI, alcohol consumption,cigarette smoking and blood pressure in both ethnic groups.Conclusions: There was no significant difference in either genotypic orallelic frequencies between Mulao and Han. The genotypic and allelicfrequencies were different between Han males and females. The association of KLF14rs4731702SNP and serum lipid levels is different between the twoethnic groups, or between males and females. There may be an ethnic-and/orsex-specific association of the KLF14rs4731702SNP and serum lipid levels.