Polymorphism analysis of APOE and SLCO1B1 genes in Meizhou area of southern China

Background APOE and SLCO1B1 genetic polymorphisms are relevant in statin pharmacokinetics.Objective Aim of this study was to investigate the polymorphisms of APOE and SLCO1B1 gene in Meizhou area.Methods Genotying of APOE and SLCO1B1 genetic polymorphisms were conducted in 4761 individuals.Results Among two variants of SLCO1B1 in Meizhou, the frequencies of 388A>G and 521T>C allele were 74.89% and 11.54% separately. The frequency of SLCO1B1 gene hplotype 1b/ 1b was 40.37% followed by 1a/ 1b (31.93%) and 1b/ 15(14.14%). There were no significant differences between men and women in this study except SLCO1B1 521T>C ( SLCO1B1 521TT, P =0.019; SLCO1B1 521TC, P =0.028) and haplotypes 1a/ 15 of SLCO1B1 ( 1a/ 15, P=0.02). Moreover, the frequencies of APOE ɛ3/ɛ3 was 69.94%, followed by 15.77% in ɛ3/ɛ4, 11.30% in ɛ2/ɛ3, 1.56% in ɛ2/ɛ4, 1.02% in ɛ4/ ɛ4 and 0.54% in ɛ2/ɛ2, with considerably higher rate of allele ɛ3 (83.48%).Conclusions The population of Meizhou has different distribution feature. This study provides a reference to optimize the individualization of drug use in this area. Associations of the SLCO1B1 Polymorphisms With Hepatic Function, Baseline Lipid Levels, and Lipid-lowering Response to Simvastatin in

year's medication mostly for adverse drug reactions (ADRs) (Ho et al., 2008) mainly manifest as statin-induced myopathy and rhabdomyolysis. According to previous researches, the development of statin-induced ADRs and lipid-lowering effect are usually connected with the action of hepatic organic anion-transporting polypeptide (OATP) encoded by SLCO1B1 gene (Link et al., 2008).
The polymorphisms of the SLCO1B1 and APOE genes are important for guiding the individualization of statins, thus, it is necessary to explore the genotype distribution of different ethnic and different regions. With a total area of 15,876 km 2 and a population of 5.44 million, Meizhou area is situated in the northeast of Guangdong Province, bordering Fujian Province to northeast and Jiangxi Province to northeast.
Hakka population is known as an intriguing Han Chinese population accounted for the vast majority in Meizhou residents. The Hakkas living in a mixed environmentally and small inhabited lifestyle makes many genetic distribution of frequency in this region comparatively distinctive (Li, 2014). However, Meizhou area lacks sufficient data on SLCO1B1 and APOE gene polymorphisms to guide the use of statins.

Population Samples
In this study, a total of 4,761 individuals were collected, including 2949 (

Plasma lipid measurements
A blood sample of about 3 ml was taken from the subject for examination of blood lipid levels. Plasma is supposed to isolate and store at -80℃ for further analysis.

Statistical analysis
All analysis was conducted using SPSS statistical software version 21.0. The study sample alleles and genotype frequencies were estimated with a gene counting method and descriptive statistics were expressed as mean ± standard deviation (SD) for continuous variables and percentages for categorical variables. Comparing the genotype and allele frequencies with Chi-square and Independent-Samples T-Test. P < 0.05 is considered statistically significant.

Population characteristics
Genetic polymorphisms of SLCO1B1 and APOE were studied in 4761 subjects in total, including 2949 males and 1812 females. The vast majority of these individuals are native to Meizhou area. As shown in Table 1 the average age of the subjects was 65.70±11.86 years, with 65.06±11.82 years for males and 66.76±11.84 years for females. Comparing the lipid levels of males and females, the P values were all less than 0.01, and the difference was statistically significant.
The differences between man and woman in haplotypes of GT (*1B) and GC (*15) were significantly statistical (Table 3).

Distribution of SLCO1B1 allele frequencies among major study populations
We compared the estimated SLCO1B1 allele frequency here with previous reports published in other ethnic populations (Table 5). Geek, German, Indian (North) and Macedonian manifest the relatively lower rate of G allele in G388A, less than 50%, whereas Thailand and Chinese population show higher than former, generally above 70%. By contrast, the allele frequency exhibits little difference in SLCO1B1 gene 521T>C.

Discussion
Statins, as a class of lipid-lowering drugs that competitively inhibit HMG-CoA reductase, have become the most common drug to treat the dyslipidemia and to promote primary and secondary prevention against cardiovascular events (Miller & Kung, 2018). Nonetheless, despite of the undoubted clinical benefits, the efficacy and adverse effect of statins present individual difference (Feng et al., 2012;Hamilton-Craig, 2001). To a certain extent, genetic polymorphisms of SLCO1B1 and APOE genes could be responsible for the lipid-lowering effects and the adverse drug reactions (ADRs) of statin treatment (Rocha et al., 2018;Zhong et al., 2018).
The APOE genetic polymorphism studied in this investigation illustrated that ɛ3 was the most common allele of APOE gene, accounting for 83.33%, which was consistent with most studies(Griffin et al.; Marais, 2019). This indicates that the APOE allele frequencies in Meizhou area were similar to that of the Chinese-Northeast (Zhou et al., 2005), Chinese-Jinangsu Han (Liang et al., 2009) and Chinese-Kunming Han (Tang et al., 2005), while the ɛ4 allele frequency in Meizhou area is lower than that in Chinese-Shanghai(Yang et al., 2003).
As living and eating conditions get better and better, more and more people have a tendency to develop hyperlipermia so much as increase the risk of cardiovascular disease. Statins have lipid-lowering effect, with different efficacy and side effects in different person. A large part of the cause is related to genetic polymorphism, including SLCO1B1 gene and APOE gene. This study obtained more credible results by analyzing the polymorphisms of APOE and SLCO1B1 genes in the large population of Meizhou area to guide the clinical implementation of precision medicine.

Conclusions
The polymorphisms of APOE and SLCO1B1 genes in Meizhou area were analyzed.
This study provides a reference for personalized meditation in this region.

Patient consent for publication
Prior to sample collection, written informed consent was obtained from the patients or their guardians, and patient/study subject privacy was carefully protected.

None.
myopathy: a proof-of-concept study using the clinical practice research datalink.  Tables   Table 1 Clinical