Al-Bustan Suzanne A, Al-Serri Ahmad, Annice Babitha G, Alnaqeeb Majed A, Al-Kandari Wafa Y, Dashti Mohammed
Department of Biological Sciences, Faculty of Science, Kuwait University, Kuwait City, Kuwait.
Unit of Human Genetics, Department of Pathology, Faculty of Medicine, Kuwait University, Hawalli Governate, Kuwait.
PLoS One. 2018 Feb 13;13(2):e0192617. doi: 10.1371/journal.pone.0192617. eCollection 2018.
The role interethnic genetic differences play in plasma lipid level variation across populations is a global health concern. Several genes involved in lipid metabolism and transport are strong candidates for the genetic association with lipid level variation especially lipoprotein lipase (LPL). The objective of this study was to re-sequence the full LPL gene in Kuwaiti Arabs, analyse the sequence variation and identify variants that could attribute to variation in plasma lipid levels for further genetic association. Samples (n = 100) of an Arab ethnic group from Kuwait were analysed for sequence variation by Sanger sequencing across the 30 Kb LPL gene and its flanking sequences. A total of 293 variants including 252 single nucleotide polymorphisms (SNPs) and 39 insertions/deletions (InDels) were identified among which 47 variants (32 SNPs and 15 InDels) were novel to Kuwaiti Arabs. This study is the first to report sequence data and analysis of frequencies of variants at the LPL gene locus in an Arab ethnic group with a novel "rare" variant (LPL:g.18704C>A) significantly associated to HDL (B = -0.181; 95% CI (-0.357, -0.006); p = 0.043), TG (B = 0.134; 95% CI (0.004-0.263); p = 0.044) and VLDL (B = 0.131; 95% CI (-0.001-0.263); p = 0.043) levels. Sequence variation in Kuwaiti Arabs was compared to other populations and was found to be similar with regards to the number of SNPs, InDels and distribution of the number of variants across the LPL gene locus and minor allele frequency (MAF). Moreover, comparison of the identified variants and their MAF with other reports provided a list of 46 potential variants across the LPL gene to be considered for future genetic association studies. The findings warrant further investigation into the association of g.18704C>A with lipid levels in other ethnic groups and with clinical manifestations of dyslipidemia.
不同种族间的基因差异在不同人群血浆脂质水平变化中所起的作用是一个全球健康问题。几个参与脂质代谢和转运的基因是与脂质水平变化存在基因关联的有力候选基因，尤其是脂蛋白脂肪酶（LPL）。本研究的目的是对科威特阿拉伯人群的整个LPL基因进行重测序，分析序列变异，并鉴定可能导致血浆脂质水平变化的变异，以便进一步进行基因关联研究。通过桑格测序法对来自科威特的一个阿拉伯族群的样本（n = 100）进行分析，检测其跨越30 Kb的LPL基因及其侧翼序列的序列变异。共鉴定出293个变异，包括252个单核苷酸多态性（SNP）和39个插入/缺失（InDel），其中47个变异（32个SNP和15个InDel）对科威特阿拉伯人来说是新发现的。本研究首次报告了一个阿拉伯族群中LPL基因座的序列数据以及变异频率分析，其中一个新的“罕见”变异（LPL:g.18704C>A）与高密度脂蛋白（HDL）（B = -0.181；95%可信区间（-0.357，-0.006）；p = 0.043）、甘油三酯（TG）（B = 0.134；95%可信区间（0.004 - 0.263）；p = 0.044）和极低密度脂蛋白（VLDL）（B = 0.131；95%可信区间（-0.001 - 0.263）；p = 0.043）水平显著相关。将科威特阿拉伯人的序列变异与其他人群进行比较，发现其在SNP数量、InDel数量以及LPL基因座上变异数量的分布和次要等位基因频率（MAF）方面相似。此外，将鉴定出的变异及其MAF与其他报告进行比较，提供了一份LPL基因上46个潜在变异的清单，供未来的基因关联研究参考。这些发现值得进一步研究g.18704C>A与其他种族脂质水平以及血脂异常临床表现之间的关联。
