PeerJ (Sep 2024)
Association of HMGCR rs17671591 and rs3761740 with lipidemia and statin response in Uyghurs and Han Chinese
Abstract
Background Dyslipidemia plays a very important role in the occurrence and development of cardiovascular disease (CVD). Genetic factors, including single nucleotide polymorphisms (SNPs), are one of the main risks of dyslipidemia. 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is not only the rate-limiting enzyme step of endogenous cholesterol production, but also the therapeutic target of statins. Methods We investigated 405 Han Chinese and 373 Uyghur people who took statins for a period of time, recorded their blood lipid levels and baseline data before and after oral statin administration, and extracted DNA from each subject for SNP typing of HMGCR rs17671591 and rs3761740. The effects of HMGCR rs17671591 and rs3761740 on lipid levels and the effect of statins on lipid lowering in Han Chinese and Uyghur ethnic groups were studied. Results In this study, for rs17671591, the CC vs. TT+CT model was significantly correlated with the level of LDL-C before oral statin in the Uyghur population, but there were no correlations between rs17671591 and the level of blood lipid before oral statin in the Han population. The CC vs. TT+CT and CT vs. CC+TT models were significantly correlated with the level of LDL-C after oral statin in the Uyghur population. There was no significant correlation between rs3761740 with blood lipids before and after oral statin in the Han population. For rs3761740, before oral statin, the CC vs. AA+CA model was significantly correlated with the level of LDL-C, and the CA vs. CC+AA model was significantly correlated with the level of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and non-high density lipoprotein cholesterol (HDL-C) in the Uyghur population. After oral statin, the CC vs. AA+CA and CA vs. CC+AA models were significantly correlated with the level of TC, LDL-C, and apolipoprotein (APOB), and the C vs. A model was significantly correlated with the level of TC, triglyceride (TG), LDL-C, and APOB in the Uyghur population. Particularly, the CT vs. CC+TT model of rs17671591 was significantly correlated with the changes of LDL-C after oral statin in the Uyghur population. In this study, we also explored the association of rs17671591 and rs3761740 with the rate of dyslipidemia as a reference. Conclusion We found that HMGCR rs3761740 was correlated with the levels of TC, LDL-C, and non-HDL-C before and after oral statin in Uyghurs, but not with blood lipid levels in the Han population. In the Uyghur population, HMGCR rs17671591 was associated with the level of LDL-C before and after oral statin, and also affected the changes of LDL-C after oral statin.
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