Hexose-6-phosphate dehydrogenase: a new risk gene for multiple sclerosis
Antonio Alcina1, Sreeram V Ramagopalan, Oscar Fernández
1Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas, Granada, Spain.
European Journal of Human Genetics : EJHG
|November 26, 2009
Summary
A new genetic marker, rs17368528, is associated with multiple sclerosis (MS) susceptibility. This single-nucleotide polymorphism (SNP) in the H6PD gene may represent a novel target for MS research.
Area of Science:
- Genetics
- Neuroimmunology
- Human Genetics
Background:
- Genome-wide association studies (GWAS) have identified several genes linked to multiple sclerosis (MS) susceptibility.
- Previous GWAS identified 12,374 nonsynonymous single-nucleotide polymorphisms (SNPs) associated with MS risk.
Purpose of the Study:
- To validate the association of 19 specific SNPs with MS in an independent Caucasian cohort from Southern Spain.
- To investigate the potential role of the hexose-6-phosphate dehydrogenase (H6PD) gene in MS pathogenesis.
Main Methods:
- Genotyping of 19 SNPs in 732 MS patients and 974 controls from Spain.
- Replication of significant findings in an independent cohort of 1318 MS patients from the Canadian Collaborative Project.
- Analysis of SNP rs17368528's location and its potential impact on H6PD gene function.
Main Results:
- The rs17368528 polymorphism showed a significant association with MS in the Spanish cohort (P=0.04, OR=0.801).
- This association was successfully replicated in the Canadian cohort (P=0.04, OR=0.838).
- The rs17368528 SNP results in a proline-to-leucine amino acid substitution in the H6PD gene.
Conclusions:
- The study confirms the association of the rs17368528 locus with MS susceptibility.
- H6PD is identified as a novel candidate gene for multiple sclerosis.
- Genetic variations in H6PD may influence MS risk, potentially through altered enzyme activity.
Related Concept Videos
01:29Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
01:11Genetic Lingo
Overview
01:11Genome-wide Association Studies-GWAS
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
01:19Multiple Sclerosis l: Introduction
Multiple sclerosis is a chronic autoimmune disease of the central nervous system (CNS) that affects the brain, spinal cord, and optic nerves. It is an inflammatory demyelinating disorder and a leading cause of neurological disability in young adults.EpidemiologyMS commonly begins between 20 and 40 years of age and is twice as common in women. Its exact cause remains unclear, but genetic susceptibility contributes, with higher risk in first-degree relatives and identical twins. A greater...
02:32Exon Recombination
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Exon shuffling follows “splice frame rules.” Each exon has three reading...
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...