Related Experiment Videos

Novel association of a PROC variant with ischemic stroke in a Chinese Han population

Xuan Lu1, Liang Tang, Kang Xu

  • 1Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Human Genetics
|September 15, 2012
PubMed

Insights

A novel genetic variant in the protein C gene (PROC c.574_576del) is linked to an increased risk of ischemic stroke (IS) in the Chinese Han population. This variant also reduces the anticoagulant activity of protein C (PC).

Area of Science:

  • Genetics
  • Cardiovascular Medicine
  • Biochemistry

Background:

  • Protein C (PC) is a key anticoagulant enzyme, but its role in ischemic stroke (IS) susceptibility is debated.
  • Genetic factors influencing PC function may impact IS risk.

Purpose of the Study:

  • To investigate the association between genetic variants in the human protein C gene (PROC) and ischemic stroke (IS) susceptibility.
  • To evaluate the functional impact of identified PROC variants on PC anticoagulant activity.

Main Methods:

  • Sequencing of all PROC exons and untranslated regions to identify variants.
  • Case-control study in Chinese Han population (788 IS patients, 1,200 controls), with replication (262 IS patients, 288 controls).
  • Functional assays to assess the anticoagulant activity of protein C in variant carriers.

Main Results:

  • A novel three-nucleotide deletion variant (PROC c.574_576del) was identified and significantly associated with IS (OR 2.56, P=0.001).
  • The association remained significant for lacunar and cardioembolic stroke subtypes.
  • Functional studies revealed significantly reduced anticoagulant activity of PC in c.574_576del carriers.

Conclusions:

  • The PROC c.574_576del variant is a potential genetic determinant for increased ischemic stroke risk.
  • This variant is associated with diminished protein C anticoagulant activity.

Related Concept Videos

Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
Hemorrhagic Stroke ll: Pathophysiology01:29

Hemorrhagic Stroke ll: Pathophysiology

A hemorrhagic stroke develops when a cerebral blood vessel ruptures, allowing blood to escape into the surrounding brain tissue, as in intracerebral hemorrhage (ICH), or into the subarachnoid space, as in subarachnoid hemorrhage (SAH). Because the skull is a rigid compartment, the sudden presence of extravascular blood rapidly increases intracranial pressure and compresses adjacent neural structures, leading to immediate tissue injury and impaired cerebral perfusion.Mass Effect and Primary...
Ischemic Stroke ll: Pathophysiology01:15

Ischemic Stroke ll: Pathophysiology

An ischemic stroke occurs when a cerebral blood vessel becomes obstructed, most often by a thrombus or embolus, interrupting the delivery of oxygen and glucose to brain tissue. Because neurons rely on continuous aerobic metabolism, energy failure begins within minutes of reduced perfusion. The region receiving the least blood flow becomes the infarct core, an area of irreversible cellular death. Surrounding this core lies the penumbra, a zone of hypoperfused but still viable tissue that is...
Hemorrhagic Stroke l: Introduction01:17

Hemorrhagic Stroke l: Introduction

A hemorrhagic stroke is an acute neurological event that occurs when a weakened cerebral blood vessel ruptures, allowing blood to accumulate within or around the brain. The sudden release of blood forms a focal hematoma that increases intracranial pressure, displaces neural tissue, and can obstruct cerebrospinal fluid pathways. These effects may be compounded by intraventricular extension of the hemorrhage, cerebral edema, or compression of adjacent structures, all of which contribute to...
Ischemic Stroke l: Introduction01:15

Ischemic Stroke l: Introduction

Ischemic stroke is an acute cerebrovascular condition in which blood flow to a brain region is suddenly interrupted, leading to tissue infarction. Neurons depend on continuous oxygen and glucose supply, so even brief reductions in perfusion cause energy failure, ionic imbalance, and irreversible injury. Ischemic strokes are classified into thrombotic and embolic types based on their underlying mechanisms.Thrombotic MechanismsThrombotic stroke develops when a clot forms within a cerebral artery.
Genome-wide Association Studies-GWAS01:11

Genome-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...