Al Asoom Lubna Ibrahim, Alsuwat Hind Saleh, Rafique Nazish, Al Makhaita Marwah, Alamoudi Widyan, AbdulAzeez Sayed, Borgio Jesu Francis
Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University Dammam 31441, Saudi Arabia.
Department of Genetic Research, Institute for Research and Medical Consultation (IRMC), Imam Abdulrahman Bin Faisal University Dammam 31441, Saudi Arabia.
Am J Transl Res. 2019 Jun 15;11(6):3659-3670. eCollection 2019.
The study aims to explore the genetic predispositions and molecular pathways of low cardiorespiratory fitness (VO) in young Saudi females ( = 70). Young females were grouped based on the level of VO according to the specification of the physical fitness specialist certification as low VO (< 28.9; = 19) and high VO (> 33; = 14) and genotyped for 243345 putative functional exonic variants. The -rs10037485T, -rs75380747G and -rs13695C SNPs on chromosome 5, 12 and 17, respectively were found to be the most significant among young Saudi females with low VO ( < 8.01 × 10). Linkage disequilibrium (LD) analysis among the significant SNPs ( < 0.001) have revealed risk and protective haplotypes with high degree (-value < 1.0 × 10) of LD. The most significant risk haplotypes with the low VO in young Saudi females are: Chromosome 1: -rs10800201G; -rs4657537A; rs4657583T (-value = 2.00 × 10); Chromosome 3: rs978979G; -rs7637449A; -rs111934125T; -rs9835332G (-value = 5.00 × 10) and Chromosome 17: -rs13696C; -rs1901187C (-value = 1.00 × 10). Functional Enrichment Analysis revealed that the genes with SNPs < 0.001 have significantly involved in the heart rate ( = 0.00442), body weight ( = 0.00629), breath tests ( = 0.0147), proteolysis ( = 0.00623) and cardiac muscle fiber development ( = 0.0263). In conclusion we could say that the identified genetic predispositions and gene-annotation enrichment in low VO in young Saudi females revealed that they are at high risk for developing cardiovascular complications.
该研究旨在探索沙特年轻女性(n = 70)中心血管呼吸适能(VO)较低的遗传易感性和分子途径。年轻女性根据体能专家认证规范,按照VO水平分为低VO组(< 28.9;n = 19)和高VO组(> 33;n = 14),并对243345个推定的功能性外显子变体进行基因分型。分别位于5号、12号和17号染色体上的-rs10037485T、-rs75380747G和-rs13695C单核苷酸多态性(SNP)在VO较低的沙特年轻女性中最为显著(p < 8.01 × 10)。对显著SNP(p < 0.001)进行连锁不平衡(LD)分析,发现了具有高度(p值 < 1.0 × 10)LD的风险和保护单倍型。沙特年轻女性中与低VO相关的最显著风险单倍型为:1号染色体:-rs10800201G;-rs4657537A;rs4657583T(p值 = 2.00 × 10);3号染色体:rs978979G;-rs7637449A;-rs111934125T;-rs9835332G(p值 = 5.00 × 10);17号染色体:-rs13696C;-rs1901187C(p值 = 1.00 × 10)。功能富集分析表明,SNP p < 0.001的基因显著参与心率(p = 0.00442)、体重(p = 0.00629)、呼吸测试(p = 0.0147)、蛋白水解(p = 0.00623)和心肌纤维发育(p = 0.0263)。总之,我们可以说,在沙特年轻女性中确定的低VO遗传易感性和基因注释富集表明,她们发生心血管并发症的风险很高。