Chikowore Tinashe, Sahibdeen Venesa, Hendry Liesl M, Norris Shane A, Goedecke Julia H, Micklesfield Lisa K, Lombard Zané
Division of Human Genetics, School of Pathology, Faculty of Health Sciences, National Health Laboratory Service & University of the Witwatersrand, Johannesburg, South Africa.
DST-NRF Centre of Excellence in Mathematical and Statistical Sciences (CoE-MaSS), South Africa.
J Clin Transl Endocrinol. 2019 Feb 28;16:100186. doi: 10.1016/j.jcte.2019.100186. eCollection 2019 Jun.
To evaluate the association between loss-of-function (LOF) variants (A433T/rs28362263 and C679X/rs28362286) and biomarkers of cardiometabolic risk, specifically fasting glucose and low density lipoprotein cholesterol (LDL-C) concentrations.
Our study comprised 757 male and female black South African adolescents (mean age 18.0 ± 0.5 years) who are part of the Birth to Twenty Plus Cohort and had been genotyped for the two above-mentioned variants. Anthropometric measures were completed and fasting plasma glucose and lipid analysis were performed using standard procedures.
The median and interquartile range of fasting glucose and LDL-C for the whole group were 4.60 (4.36-4.88) mmol/L and 1.67 (1.25-2.14) mmol/L, respectively. After adjusting for sex, association between the biomarkers and A443T was not significant. However, C679X carriers displayed 0.30 [95% CI (-0.57, -0.02); p = 0.035] mmol/L lower fasting glucose and 0.50 [95% CI (-0.74, -0.26); p < 0.001) mmol/L lower LDL-C concentrations compared to non-carriers.
Our results indicate for the first that the C679X variants associated with low fasting glucose levels during adolescents as had been known for LDL-C. In view that a similar finding was reported in older black South African adults, therefore, the correlation of lower fasting glucose and LDL-C levels with C679X is observed from an early age to adulthood.
评估功能丧失（LOF）变异（A433T/rs28362263和C679X/rs28362286）与心脏代谢风险生物标志物之间的关联，特别是空腹血糖和低密度脂蛋白胆固醇（LDL-C）浓度。
我们的研究包括757名南非黑人青少年（平均年龄18.0±0.5岁），他们是“从出生到二十岁以上队列”的一部分，并且已对上述两种变异进行了基因分型。完成了人体测量，并使用标准程序进行了空腹血浆葡萄糖和脂质分析。
整个组的空腹血糖和LDL-C的中位数和四分位间距分别为4.60（4.36 - 4.88）mmol/L和1.67（1.25 - 2.14）mmol/L。在调整性别后，生物标志物与A443T之间的关联不显著。然而，与非携带者相比，C679X携带者的空腹血糖降低了0.30 [95%置信区间（-0.57，-0.02）；p = 0.035] mmol/L，LDL-C浓度降低了0.50 [95%置信区间（-0.74，-0.26）；p < 0.001] mmol/L。
我们的结果首次表明，C679X变异与青少年空腹血糖水平低有关，这与LDL-C的情况相同。鉴于在南非黑人成年人中也报道了类似的发现，因此，从幼年到成年都观察到空腹血糖和LDL-C水平较低与C679X之间的相关性。
