IthaID: 3549
Names and Sequences
| Functionality: | Disease modifying mutation | Pathogenicity: | N/A |
|---|---|---|---|
| Common Name: | 27bp-VNTR | HGVS Name: | NG_011992.1:g.11166_11192[4] |
Also known as: eNOS4a/b
Comments: 27-bp repeat VNTR polymorphism, aka eNOS4a/b, in intron 4 of NOS3 gene. The wild type allele 'b' comprises five copies of 27 bp repeats. The mutant allele 'a' comprises four copies of 27 bp repeats. The eNOS4a allele associated with a higher number of neutrophils in patients with sickle cell anaemia attending the Hospital de Dona Estefânia, Lisbon (n=26). Nitric oxide exerts regulatory effects on neutrophil, with low concentrations being stimulatory [PMID: 27802215]. It associated with red blood cell disaggregation threshold (i.e.: RBC aggregates strength), which affects risk of acute chest syndrome, in individuals from Guadeloupe with sickle cell disease (SCD) (n=241) [PMID: 26142331]. It associated with risk of vaso-occlusive crisis and pulmonary hypertension in Egyptian SCD patients (100 cases; 80 control) [PMID: 26903375]. VNTR 4b_allele showed a negative association with silent cerebral infarct events in pediatric patients with sickle cell anemia of sub-Saharan African ancestry in Portugal [PMID: 32434137].
We follow the HGVS sequence variant nomenclature and IUPAC standards.
External Links
No available links
Phenotype
| Allele Phenotype (Cis): | N/A |
|---|---|
| Allele Phenotype (Trans): | N/A |
| Associated Phenotypes: |
Stroke [HP:0001297] [OMIM:601367] Pulmonary arterial hypertension [HP:0002092] [OMIM:265400] Vaso-occlusive crisis Red blood cell aggregation Abnormal neutrophil cell number [HP:0011991] |
Location
| Chromosome: | 7 |
|---|---|
| Locus: | NG_011992.1 |
| Locus Location: | 11166 |
| Size: | 27 bp |
| Located at: | NOS3 |
Other details
| Type of Mutation: | Repeat |
|---|---|
| Ethnic Origin: | Portuguese, Guadeloupean, Egyptian, sub-Saharan African |
| Molecular mechanism: | N/A |
| Inheritance: | Quantitative trait |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Ferdinand S, Connes P, Brudey L, Cita KC, Tressières B, Lemonne N, Hardy-Dessources MD, Lamarre Y, Waltz X, Etienne-Julan M, Romana M, Impact of eNOS polymorphisms on red blood cell aggregation in sickle cell disease., Blood Cells Mol. Dis. , 55(2), 151-3, 2015
- Yousry SM, Ellithy HN, Shahin GH, Endothelial nitric oxide synthase gene polymorphisms and the risk of vasculopathy in sickle cell disease., Hematology , 21(6), 359-67, 2016
- Aguiar L, Matos A, Gil Â, Afonso C, Braga L, João L, Kjollerstrom P, Faustino P, Bicho M, Inácio Â, Sickle cell anemia - Nitric oxide related genetic modifiers of hematological and biochemical parameters., Clin. Hemorheol. Microcirc. , 2016
- Silva M, Vargas S, Coelho A, Ferreira E, Mendonça J, Vieira L, Maia R, Dias A, Ferreira T, Morais A, Soares IM, Lavinha J, Silva R, Kjöllerström P, Faustino P, Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia., Blood Cells Mol Dis, 83(0), 102436, 2020