Association of mitochondrial haplogroup H with reduced risk of type 2 Diabetes among Gulf Region Arabs.

Background: Numerous studies have linked mitochondrial dysfunction to the development of type 2 diabetes (T2D) by affecting glucose-stimulated insulin secretion in pancreatic beta cells and reducing oxidative phosphorylation in insulin-responsive tissues. Given the strong genetic underpinnings of T2D, research has explored the connection between mitochondrial DNA haplogroups, specific variants, and the risk and comorbidities of T2D. For example, haplogroups F, D, M9, and N9a have been linked to an elevated risk of T2D across various populations.

allele frequencies and implications for pharmacogenetics in the Kuwaiti population.

Unlabelled: This study explores the frequency of human leukocyte antigen (HLA) genes, particularly alleles, within the Kuwaiti population. We aim to identify alleles with known associations to adverse drug reactions (ADRs) based on existing literature. We focus on the gene due to its well-documented associations with severe cutaneous adverse reactions and the extensive pharmacogenetic research supporting its clinical relevance.

Evaluation of HLA typing content of next-generation sequencing datasets from family trios and individuals of arab ethnicity.

HLA typing is a critical tool in both clinical and research applications at the individual and population levels. Benchmarking studies have indicated HLA-HD as the preferred tool for accurate and comprehensive HLA allele calling. The advent of next-generation sequencing (NGS) has revolutionized genetic analysis by providing high-throughput sequencing data.

Identification of potential regulatory mechanisms and therapeutic targets for lung cancer.

Lung cancer poses a significant health threat globally, especially in regions like India, with 5-year survival rates remain alarmingly low. Our study aimed to uncover key markers for effective treatment and early detection. We identified specific genes related to lung cancer using the BioXpress database and delved into their roles through DAVID enrichment analysis.

variants beyond type 1 and type 2 diabetes: exploring clinical diversity and epigenetic associations in Arab cohorts.

gene, encoding hepatocyte nuclear factor 6, is involved in pancreas and liver development. mutations impair the function of pancreatic β-cells and control a transcriptional/epigenetic machinery regulating endocrine development. Homozygous nonsense and missense mutations at _p.

Association between alleles, haplotypes, and amino acid variations in HLA class II genes and type 1 diabetes in Kuwaiti children.

Type 1 diabetes (T1D) is a complex autoimmune disorder that is highly prevalent globally. The interactions between genetic and environmental factors may trigger T1D in susceptible individuals. HLA genes play a significant role in T1D pathogenesis, and specific haplotypes are associated with an increased risk of developing the disease.

Disruption in the regulation of casein kinase 2 in circadian rhythm leads to pathological states: cancer, diabetes and neurodegenerative disorders.

Introduction: Circadian rhythm maintains the sleep-wake cycle in biological systems. Various biological activities are regulated and modulated by the circadian rhythm, disruption of which can result in onset of diseases. Robust rhythms of phosphorylation profiles and abundances of PERIOD (PER) proteins are thought to be the master keys that drive circadian clock functions.

Signatures of purifying selection and site-specific positive selection on the mitochondrial DNA of dromedary camels (Camelus dromedarius).

The two species of the Old World Camelini tribe, dromedary and Bactrian camels, show superior adaptability to the different environmental conditions they populate, e.g. desert, mountains and coastal areas, which might be associated with adaptive variations on their mitochondrial DNA.

Frequency of functional exonic single-nucleotide polymorphisms and haplotype distribution in the SLCO1B1 gene across genetic ancestry groups in the Qatari population.

Organic anion transporting polypeptides (OATP), which are encoded by SLCO genes, participate in the hepatic elimination of drugs and xenobiotics. SLCO1B1 is an important pharmacogenomic gene (encoding OATP1B1) associated with response to the uptake of endogenous compounds, such as statin and bilirubin. Ethnicity of the patient modulates the response to these drugs; the frequency and haplotype data for SLCO1B1 genetic variants in the Arab population is lacking.

Distribution of Alleles and Haplotypes in Qatari: Recommendation for Establishing Pharmacogenomic Markers Screening for Drug Hypersensitivity.

Human leukocyte antigen (HLA) proteins are present at the cellular surface of antigen-presenting cells and play a crucial role in the adaptive immune response. Class I genes, specifically certain alleles, are associated with adverse drug reactions (ADRs) and are used as pharmacogenetic markers. Although ADRs are a common causes of hospitalization and mortality, the data on the prevalence of pharmacogenetics markers in Arab countries are scarce.

Differentially methylated and expressed genes in familial type 1 diabetes.

There has recently been a growing interest in examining the role of epigenetic modifications, such as DNA methylation, in the etiology of type 1 diabetes (T1D). This study aimed to delineate differences in methylation patterns between T1D-affected and healthy individuals by examining the genome-wide methylation of individuals from three Arab families from Kuwait with T1D-affected mono-/dizygotic twins and non-twinned siblings. Bisulfite sequencing of DNA from the peripheral blood of the affected and healthy individuals from each of the three families was performed.

Leptin rs7799039 polymorphism is associated with multiple sclerosis risk in Kuwait.

Background: Leptin association with Multiple sclerosis (MS) pathogenesis and MS related clinical characteristics is inconsistent. Here, we investigated whether two common variants in leptin (LEP) and leptin receptor (LEPR) genes influence MS risk and leptin levels in MS patients.

Methods: In a case-control study including 169 MS patients and 100 controls we examined the association of leptin in MS.

A novel LPL intronic variant: g.18704C>A identified by re-sequencing Kuwaiti Arab samples is associated with high-density lipoprotein, very low-density lipoprotein and triglyceride lipid levels.

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.

Identification of a rare germline NBN gene mutation by whole exome sequencing in a lung-cancer survivor from a large family with various types of cancer.

Nijmegen breakage syndrome is an autosomal recessive disorder caused by biallelic mutation in NBN gene. It is characterized by microcephaly, growth retardation, immuno-deficiency and cancer predisposition. The monoallelic carriers of NBN gene are also reported to be at increased risk of developing various types of malignancy.

Dissecting the genetic components of a quantitative trait locus for blood pressure and renal pathology on rat chromosome 3.

Background: We have previously confirmed the importance of rat chromosome 3 (RNO3) genetic loci on blood pressure elevation, pulse pressure (PP) variability and renal pathology during salt challenge in the stroke-prone spontaneously hypertensive (SHRSP) rat. The aims of this study were to generate a panel of RNO3 congenic sub-strains to genetically dissect the implicated loci and identify positional candidate genes by microarray expression profiling and analysis of next-generation sequencing data.

Method And Results: A panel of congenic sub-strains were generated containing Wistar-Kyoto (WKY)-introgressed segments of varying size on the SHRSP genetic background, focused within the first 50 Mbp of RNO3.

Identification of a common molecular pathway in hypertensive renal damage: comparison of rat and human gene expression profiles.

Background: There is a common structural progression in hypertensive renal damage with early arterial damage and fibrosis in the juxtamedullary cortex.

Method: The present investigation identifies a common pathway using three-gene expression profiles from hypertensive rat models: 60-week-old spontaneously hypertensive rat (SHR), salt-loaded stroke-prone SHR (SHRSP), and the non-clipped kidney after 24 weeks of two-kidney, one-clip hypertension (2K1C). Kidney damage was scored using a specialized system.

Introgressed chromosome 2 quantitative trait loci restores aldosterone regulation and reduces response to salt in the stroke-prone spontaneously hypertensive rat.

Background: The genetic contribution to salt-sensitivity in hypertension remains unclear. We have previously identified a quantitative trait locus on chromosome 2 in stroke-prone spontaneously hypertensive rats (SHRSPs) responsible for an increase in SBP in response to a salt challenge. This response is blunted in the congenic SHRSP strain with the Wistar-Kyoto (WKY) chromosome 2 region (10 cM) introgressed (SP.