Key result
HMGCR rs12916 CC linked to ~108% higher residual LDL-C risk on statins in premature triple-vessel disease.
Why the study?
The association of HMGCR and NPC1L1 gene polymorphisms with residual cholesterol risk in premature triple-vessel disease patients treated with statins was unclear.
Are HMGCR and NPC1L1 gene polymorphisms associated with residual cholesterol risk in patients with premature triple-vessel disease treated with moderate-intensity statins?
Observational (n=609)
No
Are HMGCR and NPC1L1 gene polymorphisms associated with residual cholesterol risk in patients with premature triple-vessel disease treated with moderate-intensity statins?
Odds Ratio: 2.08 (95% CI 1.16–3.75)
p-value: p=0.015
The variant homozygous CC of rs12916 within the HMGCR gene is associated with a significantly higher risk of residual cholesterol risk in premature triple-vessel disease patients on moderate-intensity statins, suggesting a genetic basis for statin response variability.
Supports HMGCR genotyping as a residual-risk marker; hypothesis-generating and should not yet change statin practice.
BACKGROUND: To investigate the association of HMGCR and NPC1L1 gene polymorphisms with residual cholesterol risk (RCR) in patients with premature triple-vessel disease (PTVD). METHODS: Three SNPs within HMGCR including rs12916, rs2303151, and rs4629571, and four SNPs within NPC1L1 including rs11763759, rs4720470, rs2072183, and rs2073547 were genotyped. RCR was defined as achieved low-density lipoprotein cholesterol (LDL-C) concentrations after statins higher than 1.8 mmol/L (70 mg/dL). RESULTS: Finally, a total of 609 PTVD patients treated with moderate-intensity statins were included who were divided into two groups: non-RCR group (n = 88) and RCR group (n = 521) according to LDL-C concentrations. Multivariate logistic regression showed the homozygotes for the minor allele of rs12916 within HMGCR gene (CC) were associated with a 2.08 times higher risk of RCR in recessive model [odds ratio (OR): 2.08, 95% confidence interval (CI): 1.16-3.75]. In codominant model, the individuals homozygous for the minor allele of rs12916 (CC) were associated with a 2.26 times higher risk of RCR (OR: 2.26, 95% CI: 1.16-4.43) while the heterozygous individuals (CT) were not, compared with the individuals homozygous for the major allele of rs12916 (TT). There was no significant association between the SNPs within NPC1L1 gene and RCR in various models. CONCLUSIONS: We first reported that the variant homozygous CC of rs12916 within HMGCR gene may incur a significantly higher risk of RCR in PTVD patients treated with statins, providing new insights into early individualized guidance of precise lipid-lowering treatment.
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Li et al. (2023) conducted an observational in Premature triple-vessel disease (PTVD) (n=609). HMGCR rs12916 CC genotype vs. HMGCR rs12916 CT or TT genotypes was evaluated on Residual cholesterol risk (RCR), defined as achieved LDL-C > 1.8 mmol/L after statins (OR 2.08, 95% CI 1.16-3.75, p=0.015). The variant homozygous CC of rs12916 within the HMGCR gene was associated with a 2.08 times higher risk of residual cholesterol risk (LDL-C > 1.8 mmol/L) in premature triple-vessel disease patients treated with statins.
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