NOS1 rs35567595: Nitric Oxide Synthase and Allergy Pathways
The rs35567595 polymorphism is a genetic variant situated within the neuronal nitric oxide synthase 1 (NOS1) gene. Published pulmonary and genetic research links variants in this locus with altered levels of fractional exhaled nitric oxide (FeNO), an established biomarker of airway inflammation in atopic diseases such as allergic asthma. The overall strength of evidence for this specific polymorphism is classified as moderate, representing a statistical modifier of airway inflammation rather than a causative disease determinant.
What each genotype means
Typical nitric oxide profile
This genotype represents the common baseline for the NOS1 variant. Research indicates that NOS1 influences the production of nitric oxide in the airways, which is a factor in inflammatory pathways. Individuals with this genotype generally show standard levels of exhaled nitric oxide compared to those with the alternative allele.
This is the most common genotype observed across most global populations.
Intermediate nitric oxide profile
Carrying one copy of the minor allele may result in intermediate levels of nitric oxide output compared to the homozygous states. Because NOS1 activity is linked to inflammatory responses in the airways, this genotype may contribute to variability in how your body manages nitric oxide levels. Please discuss any concerns regarding respiratory health or allergic symptoms with your clinician.
Carried by a significant portion of the population, with the minor allele frequency typically ranging between 10% and 20%.
Varied nitric oxide output
This genotype is associated with potential differences in the regulation of nitric oxide synthase, which plays a role in inflammatory pathways. Studies suggest that variations in the NOS1 gene can influence the concentration of nitric oxide in exhaled air, a marker often studied in the context of asthma and allergic conditions. As this is a complex trait, please consult with a healthcare provider to interpret these findings in the context of your personal health history.
This genotype is less common, reflecting the lower frequency of the minor allele in most ancestral groups.
Genomic Location and Variant Characteristics
The rs35567595 polymorphism resides on human chromosome 12 within the NOS1 (nitric oxide synthase 1) gene. As cataloged in standard human reference genomes and dbSNP, the locus reflects a non-coding nucleotide variation within the extensive genomic footprint of the gene. NOS1 spans more than 150 kilobases of genomic DNA and encompasses numerous exons and introns subject to complex transcriptional regulation. Variants residing in non-coding intronic and regulatory domains of NOS1 can influence the efficiency of pre-mRNA splicing, secondary transcript stability, or transcription factor binding affinity. In genetic research, rs35567595 is typically evaluated as a diallelic marker that tracks alongside neighboring functional variants or microsatellite regions implicated in mucosal nitric oxide production.
Biological Function of the NOS1 Gene
The NOS1 gene encodes neuronal nitric oxide synthase (nNOS), an enzyme that catalyzes the oxidation of L-arginine to produce nitric oxide (NO) and L-citrulline. While historically recognized for its physiological roles in the central and peripheral nervous systems, nNOS is also constitutively expressed in human respiratory tissues, including the airway epithelium, bronchial smooth muscle, and inhibitory non-adrenergic non-cholinergic (iNANC) nerves supplying the pulmonary tract. In the respiratory tree, nitric oxide produced by constitutive synthases functions as a crucial mediator of non-adrenergic bronchodilation, ciliary beat frequency, and host mucosal homeostasis. Dysregulation of constitutive NOS expression can lead to aberrant local concentrations of nitric oxide, altering baseline vascular tone and local airway reactivity.
Association with Airway Inflammation and Atopic Disease
In pulmonary medicine, fractional exhaled nitric oxide (FeNO) serves as an objective non-invasive biomarker for type 2 airway inflammation commonly seen in atopic asthma and allergic airway disorders. Clinical association studies have repeatedly implicated polymorphisms across the NOS1 locus in the modulation of baseline exhaled NO concentrations and individual susceptibility to atopic phenotypes. Studies evaluating NOS1 variations, including rs35567595 and closely linked markers, show moderate evidence that carriers of specific alleles exhibit altered baseline nitric oxide synthesis and differing degrees of airway hyperresponsiveness. However, observed effect sizes are modest, and outcomes frequently demonstrate population heterogeneity, emphasizing that rs35567595 acts as one component in a polygenic network modulated by environmental allergens.
Population Distribution and Ancestry Trends
According to population genomics data from public databases such as gnomAD and dbSNP, rs35567595 displays a minor allele frequency typically falling between 0.10 and 0.20 across diverse global ancestral cohorts. The major allele is widely shared among African, European, and Asian reference populations, while minor allele prevalence exhibits subtle geographical variations. Because genetic linkage disequilibrium patterns around NOS1 can vary significantly between populations with different ancestral histories, the statistical association between rs35567595 and pulmonary traits may differ across global cohorts. Consequently, findings identified in specific clinical populations cannot be universally extrapolated without considering local genomic backgrounds.
Clinical Utility and Interpretation Limits
Genotype information for rs35567595 is strictly educational and does not constitute a diagnostic test for asthma, allergic rhinitis, or any other medical condition. A genotype associated with higher or lower baseline exhaled nitric oxide does not mean an individual is guaranteed to develop atopic disease, nor does a standard genotype rule it out. Clinical diagnostics rely on comprehensive evaluations, including spirometry, clinical allergy testing, and direct physical examination. Genetic variants in the NOS pathway should never be used as a reason to alter, start, or discontinue any prescribed respiratory therapies or anti-inflammatory inhalers without direct guidance from a qualified physician.
How common is this variant?
The minor allele frequency for rs35567595 is approximately 0.10 to 0.20 across diverse ancestral populations in global sequencing projects. The vast majority of individuals carry at least one copy of the common reference allele.
Frequently asked questions
What is the rs35567595 variant?
The rs35567595 variant is a single-nucleotide polymorphism located in the human NOS1 gene on chromosome 12. It represents a common genetic sequence difference evaluated in research on airway biology and inflammatory response markers.
Does having the rs35567595 variant mean I will get asthma?
No, rs35567595 is not a causative mutation and cannot diagnose asthma or allergies. It is merely a modest statistical modifier of nitric oxide production, and the development of allergic disease depends on complex interactions between dozens of genes and environmental triggers.
How does NOS1 relate to allergic airway diseases?
The NOS1 gene produces neuronal nitric oxide synthase, which synthesizes nitric oxide in respiratory tissues to regulate airway tone and mucosal health. Variations in this gene can influence the baseline levels of exhaled nitric oxide, which is an important clinical biomarker used to assess allergic airway inflammation.
Should I change my allergy or asthma medication based on this result?
No. Genetic testing for rs35567595 is not a validated pharmacogenetic tool and must never be used to alter medical treatments. Always discuss any questions about your respiratory symptoms, inhalers, or allergy medications directly with your physician.
Sources & further reading
Educational information only, last refreshed 9/6/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Functional intronic variant in nitric oxide synthase 1 linked to periodic limb movements, sleep fragmentation, and restless legs syndrome predisposition.
Intronic variant in the NOS1 gene, which has been investigated for associations with atopy and IgE-mediated allergic responses in various populations.