Genetics of diabetic kidney disease: A follow-up study in the Arab population of the United Arab Emirates

Background: Two genome-wide association studies in European and Japanese populations reported on new loci for diabetic kidney disease (DKD), including FTO. In this study, we have replicated these investigations on a cohort of 410 Type 2 diabetes mellitus (T2DM) patients of Arab origin from the United Arab Emirates (UAE). Methods and Results: The cohort included 145 diabetic patients diagnosed with DKD and 265 diabetics free of the disease. In general, we were able to confirm the association between the FTO locus and DKD, as reported in the Japanese population. Specifically, there were significant associations with two single nucleotide polymorphisms (SNPs), namely rs1421086 (p =.013, OR = 1.52 depending on allele G, 95% CI: 1.09–2.11) and rs17817449 (p =.0088, OR = 1.55 depending on allele C, 95% CI: 1.12–2.14) of the FTO locus. Both SNPs were in linkage disequilibrium with rs56094641, also as reported in the Japanese population. While the alleles of both SNPs, which increase the risk of DKD, were associated with higher Body Mass Index (BMI), their associations with DKD were independent of the BMI effects. Conclusions: This study confirms that FTO is a multiethnic locus for DKD which is independent from any influence of BMI and/or obesity

Clinical and genetic associations of renal function and diabetic kidney disease in the United Arab Emirates: A cross-sectional study

OBJECTIVES: Within the Emirati population, risk factors and genetic predisposition to diabetic kidney disease (DKD) have not yet been investigated. The aim of this research was to determine potential clinical, laboratory and reported genetic loci as risk factors for DKD. RESEARCH DESIGN AND METHODS: Four hundred and ninety unrelated Emirati nationals with type 2 diabetes mellitus (T2DM) were recruited with and without DKD, and clinical and laboratory data were obtained. Following adjustments for possible confounders, a logistic regression model was developed to test the associations of 63 single nucleotide polymorphisms (SNPs) in 43 genetic loci with DKD (145 patients with DKD and 265 without DKD). Linear regression models, adjusted for age and gender, were then used to study the genetic associations of five renal function traits, including 83 SNPs with albumin-to-creatinine ratio, 92 SNPs with vitamin D (25-OH cholecalciferol), 288 SNPs with estimated glomerular filtration rate (eGFR), 363 SNPs with serum creatinine and 73 SNPs with blood urea. RESULTS: Patients with DKD, as compared with those without the disease, were mostly men (52%vs38% for controls), older (67vs59 years) and had significant rates of hypertension and dyslipidaemia. Furthermore, patients with DKD had T2DM for a longer duration of time (16vs10 years), which in an additive manner was the single factor that significantly contributed to the development of DKD (p=0.02, OR=3.12, 95% CI 1.21 to 8.02). Among the replicated associations of the genetic loci with different renal function traits, the most notable included CONCLUSIONS: Associations were found between several genetic loci and risk markers for DKD, which may influence kidney function traits and DKD in a population of Arab ancestry

Introducing the first whole genomes of nationals from the United Arab Emirates

Whole Genome Sequencing (WGS) provides an in depth description of genome variation. In the era of large-scale population genome projects, the assembly of ethnic-specific genomes combined with mapping human reference genomes of underrepresented populations has improved the understanding of human diversity and disease associations. In this study, for the first time, whole genome sequences of two nationals of the United Arab Emirates (UAE) at \u3e27X coverage are reported. The two Emirati individuals were predominantly of Central/South Asian ancestry. An in-house customized pipeline using BWA, Picard followed by the GATK tools to map the raw data from whole genome sequences of both individuals was used. A total of 3,994,521 variants (3,350,574 Single Nucleotide Polymorphisms (SNPs) and 643,947 indels) were identified for the first individual, the UAE S001 sample. A similar number of variants, 4,031,580 (3,373,501 SNPs and 658,079 indels), were identified for UAE S002. Variants that are associated with diabetes, hypertension, increased cholesterol levels, and obesity were also identified in these individuals. These Whole Genome Sequences has provided a starting point for constructing a UAE reference panel which will lead to improvements in the delivery of precision medicine, quality of life for affected individuals and a reduction in healthcare costs. The information compiled will likely lead to the identification of target genes that could potentially lead to the development of novel therapeutic modalities

Autosomal Short Tandem Repeat (STR) Variation Based on 15 Loci in a Population from the Central Region (Riyadh Province) of Saudi Arabia

INTRODUCTION: The small size of Short Tandem Repeats (STRs), their ubiquitous genome-wide distribution and polymorphic nature enhances their value in human forensic/population genetics applications. OBJECTIVES: This study aims to investigate the short tandem repeat variation based on 15 loci in a population from the central region of Saudi Arabia. METHODS: Allele frequency variation for 15 Short Tandem Repeat (STR) loci was examined in 190 unrelated Saudi volunteers. Results: This study summarizes the allele distribution in the Saudi population and compares them to other populations located in Asia, Africa, the Middle East and Europe. The standard forensic parameters of Observed Hetrozygosity (Ho), Expected Heterozygosity (He) and Gene Diversity Index (GD) were determined for the following 15 STR loci: D8S1179, D21S1, D7S820, CSF1PO, D3S1358, TH0, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S5, D5S818 and FGA. The most frequent alleles in the Saudi population were: 8 repeats (0.558) at TPOX, 12 (0.411) at D13S317, 12 (0.385) at CSF1PO, 11 (0.382) at D16D539 and 10 (0.358) at D7S820. The 15 markers utilized in this study are highly informative as evidenced by their high power of discrimination (PD) values with D2S1338, D19S433 and FGA having the highest PD values. The relationship between the Saudi population and other geographically distributed populations, assessed by a Multidimensional Scaling (MDS) plot, showed that the Saudi population clustered with groups from Yemen, Iraq, Qatar, Oman and Bahrain. CONCLUSION: TPOX, D13S317, CSF1PO, D16D539 and D7S820 markers were found suitable for forensic analysis, paternity testing and can also be used for chimerism study after allogenic bone marrow transplantation for Saudi population. On the other hand, the population admixture with other ethnic origins might explain the variable degree of genetic distances of this population and other Arab-related groups

Multicenter phase II study of sequential radioembolization-sorafenib therapy for inoperable hepatocellular carcinoma

10.1371/journal.pone.0090909PLoS ONE93-POLN

Travel ban effects on SARS-CoV-2 transmission lineages in the UAE as inferred by genomic epidemiology

Global and local whole genome sequencing of SARS-CoV-2 enables the tracing of domestic and international transmissions. We sequenced Viral RNA from 37 sampled Covid-19 patients with RT-PCR-confirmed infections across the UAE and developed time-resolved phylogenies with 69 local and 3,894 global genome sequences. Furthermore, we investigated specific clades associated with the UAE cohort and, their global diversity, introduction events and inferred domestic and international virus transmissions between January and June 2020. The study comprehensively characterized the genomic aspects of the virus and its spread within the UAE and identified that the prevalence shift of the D614G mutation was due to the later introductions of the G-variant associated with international travel, rather than higher local transmissibility. For clades spanning different emirates, the most recent common ancestors pre-date domestic travel bans. In conclusion, we observe a steep and sustained decline of international transmissions immediately following the introduction of international travel restrictions

Travel ban effects on SARS-CoV-2 transmission lineages in the UAE as inferred by genomic epidemiology

Global and local whole genome sequencing of SARS-CoV-2 enables the tracing of domestic and international transmissions. We sequenced Viral RNA from 37 sampled Covid-19 patients with RT-PCR-confirmed infections across the UAE and developed time-resolved phylogenies with 69 local and 3,894 global genome sequences. Furthermore, we investigated specific clades associated with the UAE cohort and, their global diversity, introduction events and inferred domestic and international virus transmissions between January and June 2020. The study comprehensively characterized the genomic aspects of the virus and its spread within the UAE and identified that the prevalence shift of the D614G mutation was due to the later introductions of the G-variant associated with international travel, rather than higher local transmissibility. For clades spanning different emirates, the most recent common ancestors pre-date domestic travel bans. In conclusion, we observe a steep and sustained decline of international transmissions immediately following the introduction of international travel restrictions

Distinctions in gastric cancer gene expression signatures derived from laser capture microdissection versus histologic macrodissection

<p>Abstract</p> <p>Background</p> <p>Gastric cancer samples obtained by histologic macrodissection contain a relatively high stromal content that may significantly influence gene expression profiles. Differences between the gene expression signature derived from macrodissected gastric cancer samples and the signature obtained from isolated gastric cancer epithelial cells from the same biopsies using laser-capture microdissection (LCM) were evaluated for their potential experimental biases.</p> <p>Methods</p> <p>RNA was isolated from frozen tissue samples of gastric cancer biopsies from 20 patients using both histologic macrodissection and LCM techniques. RNA from LCM was subject to an additional round of T7 RNA amplification. Expression profiling was performed using Affymetrix HG-U133A arrays. Genes identified in the expression signatures from each tissue processing method were compared to the set of genes contained within chromosomal regions found to harbor copy number aberrations in the tumor samples by array CGH and to proteins previously identified as being overexpressed in gastric cancer.</p> <p>Results</p> <p>Genes shown to have increased copy number in gastric cancer were also found to be overexpressed in samples obtained by macrodissection (LS <it>P </it>value < 10^-5), but not in array data generated using microdissection. A set of 58 previously identified genes overexpressed in gastric cancer was also enriched in the gene signature identified by macrodissection (LS <it>P </it>< 10^-5), but not in the signature identified by microdissection (LS <it>P </it>= 0.013). In contrast, 66 genes previously reported to be underexpressed in gastric cancer were enriched in the gene signature identified by microdissection (LS <it>P </it>< 10^-5), but not in the signature identified by macrodissection (LS <it>P </it>= 0.89).</p> <p>Conclusions</p> <p>The tumor sampling technique biases the microarray results. LCM may be a more sensitive collection and processing method for the identification of potential tumor suppressor gene candidates in gastric cancer using expression profiling.</p