Department of Medical Biochemistry, Amsterdam UMC, Amsterdam Cardiovascular Sciences, and Amsterdam Gastroenterology, Endocrinology and Metabolism, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Department of Physiology, Amsterdam UMC, Vrije Universiteit Medical Center, 1081 HV Amsterdam, The Netherlands.
Int J Mol Sci. 2023 Feb 22;24(5):4332. doi: 10.3390/ijms24054332.
Type 2 diabetes mellitus (T2D) is a prevalent disease often accompanied by the occurrence of dyslipidemia. Four and a half LIM domains 2 (FHL2) is a scaffolding protein, whose involvement in metabolic disease has recently been demonstrated. The association of human FHL2 with T2D and dyslipidemia in a multiethnic setting is unknown. Therefore, we used the large multiethnic Amsterdam-based Healthy Life in an Urban Setting (HELIUS) cohort to investigate FHL2 genetic loci and their potential role in T2D and dyslipidemia. Baseline data of 10,056 participants from the HELIUS study were available for analysis. The HELIUS study contained individuals of European Dutch, South Asian Surinamese, African Surinamese, Ghanaian, Turkish, and Moroccan descent living in Amsterdam and were randomly sampled from the municipality register. Nineteen FHL2 polymorphisms were genotyped, and associations with lipid panels and T2D status were investigated. We observed that seven FHL2 polymorphisms associated nominally with a pro-diabetogenic lipid profile including triglyceride (TG), high-density and low-density lipoprotein-cholesterol (HDL-C and LDL-C), and total cholesterol (TC) concentrations, but not with blood glucose concentrations or T2D status in the complete HELIUS cohort upon correcting for age, gender, BMI, and ancestry. Upon stratifying for ethnicity, we observed that only two of the nominally significant associations passed multiple testing adjustments, namely, the association of rs4640402 with increased TG and rs880427 with decreased HDL-C concentrations in the Ghanaian population. Our results highlight the effect of ethnicity on pro-diabetogenic selected lipid biomarkers within the HELIUS cohort, as well as the need for more large multiethnic cohort studies.
2 型糖尿病（T2D）是一种常见疾病，常伴有血脂异常。四个半 LIM 结构域 2（FHL2）是一种支架蛋白，其在代谢疾病中的作用最近已经得到证实。在多民族环境中，人类 FHL2 与 T2D 和血脂异常的关联尚不清楚。因此，我们使用大型多民族阿姆斯特丹城市生活环境（HELIUS）队列研究 FHL2 遗传位点及其在 T2D 和血脂异常中的潜在作用。HELIUS 研究的基线数据包含 10056 名参与者，可用于分析。HELIUS 研究包含居住在阿姆斯特丹的欧洲荷兰人、南亚苏里南人、非洲苏里南人、加纳人、土耳其人和摩洛哥人的个体，并且是从市议会登记处随机抽样的。对 19 个 FHL2 多态性进行了基因分型，并研究了它们与脂质谱和 T2D 状态的关联。我们观察到，在完全 HEILUS 队列中，七个 FHL2 多态性与糖尿病前的脂质谱相关，包括甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）以及总胆固醇（TC）浓度，但与血糖浓度或 T2D 状态无关，在对年龄、性别、BMI 和血统进行校正后。按种族分层时，我们观察到，只有两个名义上显著的关联通过了多重测试调整，即 rs4640402 与甘油三酯升高和 rs880427 与加纳人群中高密度脂蛋白胆固醇浓度降低有关。我们的结果强调了种族对 HEILUS 队列中糖尿病前选定脂质生物标志物的影响，以及需要更多的大型多民族队列研究。
