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SLCO1B1 521T > C 导致的他汀类药物诱导的肌肉疾病与阿联酋人群的前驱糖尿病、高体重指数和正常血脂谱相关。

Statin-induced myopathy SLCO1B1 521T > C is associated with prediabetes, high body mass index and normal lipid profile in Emirati population.

机构信息

College of Medicine and Research Institute for Medical and Health Sciences (RIMHS), University of Sharjah, United Arab Emirates; College of Medicine, Cairo University, Egypt.

College of Medicine and Research Institute for Medical and Health Sciences (RIMHS), University of Sharjah, United Arab Emirates.

出版信息

Diabetes Res Clin Pract. 2018 May;139:272-277. doi: 10.1016/j.diabres.2018.03.014. Epub 2018 Mar 10.

DOI:10.1016/j.diabres.2018.03.014
PMID:29534995
Abstract

BACKGROUND

Statin-induced myopathy has been linked to the C allele of a single nucleotide polymorphism (SNP) (rs4149056) of SLCO1B1 gene. This effect is more significant, but not restricted to simvastatin. Many studies have included European, American, African and Southeast Asian ancestries, but few were carried out on Middle Eastern population.

AIM

To detect the prevalence of SLCO1B1 rs4149056 (521T > C) in Emirati population.

METHOD

We recruited 282 Emiratis through the UAE National Diabetes and Lifestyle Project. Ethical approval was obtained before the study starts. Besides basic data collection, venous blood samples were collected. Fasting blood glucose, Lipid profile, and insulin levels were measured. Genotyping for rs4149056 (521T > C) was tested in triplicates through Real Time-PCR using TaqMan® Drug Metabolism Genotyping Assay. rs2306283 (388A > G) was analyzed for comparison. In addition, presence of minor alleles of both SNPs define stronger association with statin-induced myopathy.

RESULTS

The study included 282 individuals, 52.8% were males with median age of 39.5 years. 10% had Diabetes Mellitus and 23% were hypertensive. Median of body mass index (BMI) was 27.68 kg/m in males and 28.38 kg/m in females. One-hundred ninety-seven (69.9%) showed abnormal lipid profile (either increased LDL-cholesterol or triglycerides or both). For rs4149056, C allele was present in 21.3% (2.8% homozygous C and 18.4% heterozygous CT). Although homozygous C genotype prevalence was low, compared with Caucasians (4%) and Africans (0%), C allele was associated with a trend of having higher BMI and abnormal lipid profile. C allele subjects were all pre-diabetics with mean glycated hemoglobin above 6%. Mean BMI in CC, CT, and TT genotypes was 30.91 ± 4.4, 29.48 ± 4.2, 27.96 ± 5.5 kg/m respectively, with lack of such a trend observed with the different genotypes of the rs2306283 (used for comparison). Abnormal lipid profile was observed in 7/8(87.5%), 38/52(73.1%) and 152/222(70%) of the CC, CT, and TT genotypes respectively.

CONCLUSION

There is lower prevalence of statin-induced myopathy-linked C allele of rs4149056 in SLCO1B1 gene in Emirati population, compared to Caucasians and Africans. However, there is a trend of higher glycosylated hemoglobin and BMI associated with normal lipid profile in patients having this allele.

摘要

背景

他汀类药物诱导的肌病与 SLCO1B1 基因中单核苷酸多态性(SNP)(rs4149056)的 C 等位基因有关。这种影响更为显著,但不仅限于辛伐他汀。许多研究都包括欧洲、美洲、非洲和东南亚血统,但很少在中东人群中进行。

目的

检测阿联酋人群中 SLCO1B1 rs4149056(521T>C)的流行率。

方法

我们通过阿联酋国家糖尿病和生活方式项目招募了 282 名阿联酋人。在研究开始前获得了伦理批准。除了基本数据收集外,还采集了静脉血样。测量空腹血糖、血脂谱和胰岛素水平。通过 TaqMan®药物代谢基因分型检测试剂盒(Real Time-PCR)对 rs4149056(521T>C)进行了三次重复的基因分型检测。分析了 rs2306283(388A>G)进行比较。此外,两种 SNP 的次要等位基因的存在与他汀类药物诱导的肌病有更强的关联。

结果

该研究包括 282 名参与者,其中 52.8%为男性,中位年龄为 39.5 岁。10%患有糖尿病,23%患有高血压。男性的平均体重指数(BMI)为 27.68kg/m,女性为 28.38kg/m。197 名(69.9%)表现出异常的血脂谱(要么 LDL-胆固醇升高,要么甘油三酯升高,要么两者都升高)。对于 rs4149056,C 等位基因的存在率为 21.3%(2.8%为纯合子 C,18.4%为杂合子 CT)。尽管纯合子 C 基因型的患病率较低,但与高加索人(4%)和非洲人(0%)相比,C 等位基因与 BMI 和异常血脂谱升高的趋势有关。C 等位基因的受试者均为糖尿病前期患者,糖化血红蛋白平均值超过 6%。CC、CT 和 TT 基因型的平均 BMI 分别为 30.91±4.4、29.48±4.2 和 27.96±5.5kg/m,而不同基因型的 rs2306283(用于比较)则没有观察到这种趋势。CC、CT 和 TT 基因型的异常血脂谱分别为 7/8(87.5%)、38/52(73.1%)和 152/222(70%)。

结论

与高加索人和非洲人相比,阿联酋人群 SLCO1B1 基因中他汀类药物诱导的肌病相关的 rs4149056 的 C 等位基因的流行率较低。然而,在携带这种等位基因的患者中,存在与正常血脂谱相关的较高糖化血红蛋白和 BMI 的趋势。

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