Association Of The MLXIPL/TBL2rs17145738SNP And Serum Lipid Levels In The Guangxi Mulao Population

Background and Purpose: In recent years, with the rapidly application ofgenome-wide association study (GWAS) in Europe and other developedcountries, more and more lipid-related genes/loci have been identified. One ofthese novel variants is the rs17145738single nucleotide polymorphism (SNP)which is located between MLX interacting protein-like and transducin(beta)-like2(MLXIPL/TBL2) at7q11.23. It has been associated with plasma orserum lipid levels in European descent, especially with triglycerides (TG) andhigh-density lipoprotein cholesterol (HDL-C). However, the results areinconsistent in several previous GWASs. Mulao is an isolated minorities in ourcountry，and still retains the unique customs such as ethnic endogamy forthousands of year. Therefore, it is an ideal group for population genetics. It iswell known that serum lipid levels and hyperlipidemia are strongly associatedwith racial differences and genetic heterogeneity. The frequencies of somegenotypes and alleles may be different in diverse ethnic/racial groups. Thus, thecurrent study was to investigate the association of MLXIPL/TBL2rs17145738 SNP and several environmental factors with serum lipid profiles in the GuangxiMulao and Han populations.Methods: A total of649subjects of Mulao nationality and712participantsof Han nationality aged16-84years were randomly selected from our previousstratified randomized samples. The genotypes of MLXIPL/TBL2rs17145738SNP were determined by polymerase chain reaction and restriction fragmentlength polymorphism (PCR-RFLP) combined with gel electrophoresis, and thenconfirmed by direct sequencing. Statistical analysis was performed withSPSS16.0statistical software package.Results: Serum apolipoprotein (Apo) B levels were higher in Mulao than inHan (P <0.001), but the levels of total cholesterol (TC), TG, HDL-C,low-density lipoprotein cholesterol (LDL-C), ApoAI and the ratio of ApoAI toApoB were not different between Mulao and Han. There were no significantdifferences in the genotypic and allelic frequencies of the MLXIPL/TBL2rs17145738SNP between the two ethnic groups or between males and females.The levels of TG and ApoB in Mulao were different between the CT/TT and TTgenotypes (P <0.05). The T allele carriers had higher TG and ApoB levels thanthe T allele non-carriers. The levels of TC and LDL-C in Han were differentbetween the genotypes (P <0.05). The T allele carriers had higher TC andLDL-C levels than the T allele non-carriers. Subgroup analyses showed that theApoB levels were different in Mulao females but not in males and in Han malesand females (P <0.05for all). The T allele carriers in Han had higher TC,HDL-C levels and ApoAI/ApoB ratio and lower TG levels in males, and higherLDL-C levels and lower ApoAI/ApoB ratio in females than the T allelenon-carriers (P <0.05for all). Serum TC levels in the combined population of the two ethnic groups and in Han were correlated with the genotypes. Serumlipid parameters were also correlated with several environmental factors in bothethnic groups (P <0.05-0.001).Conclusion: The association of MLXIPL/TBL2rs17145738SNP and serumlipid profiles is different between the Mulao and Han populations, or betweenmales and females. This suggests that the discrepancy between the two ethnicgroups might partly result from different genetic background and environmentalfactor. There is a sex-specific association in the both ethnic groups.