ABSTRACT
Migraine, as the seventh most disabling neurological disease with 26.9% prevalence in Saudi females, lacks studies on identifying associated genes and pathways with migraines in the Arab population. This case control study aims to identify the migraine-associated novel genes and risk variants. More than 1900 Arab ancestry young female college students were screened: 103 fulfilled the ICHD-3 criteria for migraine and 20 cases confirmed in the neurology clinic were included for the study with age-matched healthy controls. DNA from blood samples were subjected to paired-end whole-exome sequencing. After quality control, 3365343 missense, frameshift, missense splice region variants and insertion-deletion (indels) polymorphisms were tested for association with migraine. Significant variants were validated using Sanger sequencing. A total of 17 (p-value 9.091 × 10-05) functional variants in 12 genes (RETNLB, SCAI, ADH4, ESPL1, CPT2, FLG, PPP4R1, SERPINB5, ZNF66, ETAA1, EXO1 and CPA6) were associated with higher migraine risk, including a stop-gained frameshift (-13-14*SX) variant in the gene RETNLB (rs5851607; p-value 3.446 × 10-06). Gene analysis revealed that half of the significant novel migraine risk genes were expressed in the temporal lobe (p-value 0.0058) of the cerebral cortex. This is the first study exploring the migraine risk of 17 functional variants in 12 genes among Saudi female migraineurs of Arab ancestry using whole-exome sequencing. Half of the significant genes were expressed in the temporal lobe, which expands migraine pathophysiology and early identification using biomarkers for research possibilities on personalised genetics.
ABSTRACT
Background: Mitochondrial DNA (mtDNA) mutations have been reported in multiple neurological diseases and helped to explain the pathophysiology of these diseases. Similarly, variations in mtDNA might exist in migraine and can explain the effect of low ATP production in the neurons on the initiation of migraine attack. Therefore, in the current study we aim to explore the association of mtDNA mutations on migraine in the Saudi population. Subjects and Methods: Over 1950 young Saudi female students were screened for migraine, among that a total of 103 satisfied the ICHD-3 criteria. However, 20 migraine cases confirmed in the neurology clinic and gave consent to participate in the study. Another 20 age-matched healthy controls were also recruited. Mitochondrial sequence variations were filtered from exome sequencing using NCBI GenBank Reference Sequence: NC_012920.1 and analysed using MITOMAP. Genes with significant single nucleotide polymorphisms (SNPs) were investigated by the gene functional classification tool DAVID and functional enrichment analysis of protein-protein interaction networks through STRING 11.5 for the most significant associated genes. Results: Genome wide analysis of the mitochondrial sequence variations between the patients with migraine and control revealed the association of 30 SNPs (p < 0.05) in the mitochondrial genome. The highest significance (p = 0.001033) was observed in a coding SNP (rs1603225278) in the CYTB gene and rs386829281 in the region of origin of replication. Twenty-four significant SNPs were in the coding region of nine (ND5, ND4, COX2, COX1, ND3, CYTB, COX3, ND2 and ND1) genes. Conclusion: This is the first study to demonstrate the association of mtDNA variations with migraine in the Saudi population. The current findings will help to highlight the significance of mtDNA mutations to migraine pathophysiology and will serve as a reference data for larger national and international studies.
ABSTRACT
BACKGROUND: Obesity is a major health threat worldwide. It predisposes individuals to diabetes, cardiovascular complications, and cancer. Genetic and environmental factors are responsible for the increasing incidence of obesity. In this study, we investigated the genetic factors associated with obesity in young Saudi women. SUBJECTS AND METHODS: In this cross-sectional study, 131 young Saudi female students were recruited. Body mass index (BMI), waist-hip ratio, blood glucose, triglyceride, cholesterol, HDL, LDL, and vitamin D3 levels of the subjects were determined. Twelve SNPs of different genes that showed a correlation with obesity in different population were tested, namely GNPDA2 (rs10938397), TCF7L2 (rs10885409), FTO (rs1477196), ADIPOQ (rs1501299), MC4R (rs17782313), ABCA1 (rs1800977), FTO (rs1861868), VDR (rs2228570), VDR (rs731236), VDR (rs7975232), ADIPOQ (rs266729), and PFPK (rs6602024). Student's t-test was conducted for all parameters. Pearson correlation was performed to identify the correlated variables. The frequencies of different risk alleles were determined by direct counting of the test allele divided by the total number of alleles and compared. RESULTS: Only two SNPs, rs1861868 of FTO and rs7975232 of VDR, of the twelve tested SNPs showed significant protective associations with the BMI with odds ratio 0.3886 (0.1761-0.8572); p 0.0192 and odds ratio 0.4563 (0.2343-0.8888); p 0.0211, respectively. CONCLUSION: The current study showed that minor alleles, "T" of FTO and "A" of VDR, might be protective factors against increased BMI in young Saudi female subjects. To elucidate this association, further studies with larger sample size involving both sexes are required.
