Vascular Inflammation & Remodeling

Promoter variant that increases CCL2 (MCP-1) transcription, amplifying monocyte recruitment to arterial walls and elevating atherosclerotic plaque risk

3'UTR variant in the NADPH oxidase p22-phox subunit affecting superoxide generation and vascular oxidative stress

Intergenic variant near MGST1 that modifies whether aspirin/NSAIDs reduce colorectal cancer risk; T allele carriers may lose the protective benefit

Intronic ALOX5AP variant in the HapA haplotype; the A allele is associated with elevated leukotriene production and increased leukotriene-mediated vascular inflammation, with population-specific associations with ischemic stroke and systemic sclerosis-related interstitial lung disease

Rare stop-gain variant in BMPR2 (p.Trp466Ter) that truncates the kinase domain via nonsense-mediated decay, causing haploinsufficiency and hereditary pulmonary arterial hypertension with incomplete penetrance and sex-dependent expression

Nonsense variant in BMPR2 introducing a premature stop codon (p.Arg321Ter) that truncates the kinase domain; hereditary cause of pulmonary arterial hypertension with incomplete penetrance and autosomal dominant inheritance

Intronic CYP2J2 tag SNP; the C allele marks a haplotype associated with reduced epoxyeicosatrienoic acid (EET) production and increased myocardial infarction risk through impaired cardioprotective vasodilation

Intergenic variant near SOX17 at 8q11 that reduces expression of this endothelial transcription factor, increasing susceptibility to intracranial aneurysm and cerebrovascular instability.

Intronic CYP2J2 variant associated with increased myocardial infarction risk and female-specific hypertension susceptibility through reduced epoxyeicosatrienoic acid (EET) production

Regulatory variant ~7 kb upstream of VEGFA linked to elevated varicose vein risk through altered vascular endothelial growth factor expression and venous wall remodeling

3' UTR variant that modulates baseline C-reactive protein levels and inflammatory status

Intronic PON2 haplotype tag; the A allele is associated with reduced intracellular antioxidant protection in vascular and renal cells, with the CC genotype conferring 32% lower risk of diabetic microalbuminuria versus AA homozygotes

Pathogenic NOTCH3 missense variant p.Arg332Cys that alters the cysteine count in EGF-like repeat 6, causing CADASIL — the most common inherited cause of ischemic stroke and vascular dementia

3'UTR variant that increases CCL2 mRNA stability via enhanced HuR binding, elevating MCP-1 protein output and monocyte recruitment in arterial inflammation

Promoter variant affecting IL-1 beta production, influencing inflammatory response and cardiovascular disease risk

Intronic ALOX5AP variant tagging the HapB risk haplotype; the A allele marks a distinct leukotriene pathway activation pattern independently associated with myocardial infarction and ischemic stroke risk

Intronic ALOX5AP haplotype tag; the common G allele marks the HapB cardiovascular risk haplotype via elevated leukotriene production, while the rare A allele confers partial protection against coronary heart disease and myocardial infarction

Intronic variant in the primary lymphangiogenesis growth factor gene; the minor A allele is protective against diabetic retinopathy and diabetic macular edema, reducing risk by ~33%

Intronic VEGFC variant independently associated with reduced diabetic retinopathy and diabetic macular edema risk; the protective T allele modulates VEGF-C-driven pathological retinal neovascularization

Regulatory variant in the CCR5 promoter that reduces CCR5 expression by ~45%; the G allele lowers surface CCR5 density on immune cells, slowing HIV disease progression, while the A allele drives higher CCR5 levels and greater monocyte recruitment to atherosclerotic plaques

Signal-peptide missense variant altering TGF-β1 secretion levels, associated with cardiovascular inflammation, myocardial fibrosis, and coronary heart disease risk

Promoter variant affecting IL-10 production — a key anti-inflammatory cytokine regulating inflammation and cardiovascular risk

Synonymous exon 2 variant that influences baseline C-reactive protein expression and inflammatory phenotypes

Intronic CFH variant that tags the complement-risk haplotype; the C allele (common, ~80% in Europeans) marks impaired complement regulation driving AMD and systemic inflammation, while the T allele is protective

Intronic CFH variant at chromosome 1q31.3 associated with AMD risk; the C allele (common globally) tags a complement-dysregulation haplotype, while the rare A allele (GRCh38 reference) is protective

Intronic TLR4 variant in the innate immune receptor gene; the A allele associates with modestly reduced vascular inflammation and lower risk of nonfatal myocardial infarction, while the common GG genotype is linked to higher atherosclerotic cerebral infarction risk

Rare missense variant in BMP9/GDF2 that impairs processing of the mature BMP9 ligand, reducing ALK1 vascular signaling and predisposing carriers to hereditary hemorrhagic telangiectasia type 5 (HHT5)

Intronic PON1 variant that modulates arylesterase activity of the HDL-bound antioxidant enzyme paraoxonase-1, influencing protection against LDL oxidation and atherosclerosis

Intronic variant in estrogen receptor alpha that alters ESR1 expression and has been associated with gestational hypertension risk and breast cancer susceptibility

Pathogenic missense variant in TGFBR2 (Leu308Pro) causing Loeys-Dietz syndrome type 2 — a connective tissue disorder with high risk of early aortic aneurysm and dissection requiring lifelong cardiovascular surveillance

Pathogenic missense variant in ALK1 kinase domain causing hereditary hemorrhagic telangiectasia type 2 (HHT2) and pulmonary arterial hypertension

Pathogenic missense variant in the cytochrome P450 1B1 enzyme that abolishes most enzyme activity, causing primary congenital glaucoma and reduced estrogen hydroxylation capacity

Pathogenic CYP1B1 missense variant (Arg469Trp) that severely reduces enzyme activity and is a leading genetic cause of primary congenital glaucoma, particularly in Middle Eastern, Iranian, and Pakistani populations

Triallelic promoter variant that strongly influences basal CRP transcription; the T (coding) and A (coding) alleles both increase CRP expression, with the A allele having the largest effect on circulating CRP levels

Promoter variant that elevates baseline C-reactive protein levels, increasing cardiovascular inflammation risk and stroke susceptibility

Promoter variant affecting interleukin-8 transcription and inflammatory burden

Intronic PON2 variant associated with variation in serum paraoxonase activity; the T allele tags a haplotype with reduced PON2-mediated antioxidant protection in vascular cells and macrophages, modestly increasing susceptibility to oxidative stress-driven atherosclerosis

Affects paraoxonase-1 enzyme activity for detoxifying organophosphates and protecting LDL from oxidation

Adipose tissue vascularization variant near VEGFA influencing fat distribution, insulin resistance, and waist-to-hip ratio with strong female-specific effects

Chromosome 9 regulatory co-variant near a lncRNA locus that co-segregates with VEGFA-pathway GWAS signals; T allele may associate with altered circulating VEGF levels influencing angiogenic capacity and vascular remodeling

Promoter polymorphism that controls PON1 gene expression — the T allele (A on the plus strand) reduces transcription factor binding, halving arylesterase activity and lowering HDL-mediated antioxidant protection against LDL oxidation.

Intronic/downstream PON1 haplotype-tagging variant associated with PON1 activity levels; the A allele tracks with lower PON1 antioxidant enzyme function on HDL, increasing vulnerability to LDL oxidation and cardiovascular risk

Promoter variant that controls PON1 transcription; the T allele reduces PON1 expression by ~2-fold, lowering the anti-atherogenic enzyme activity on HDL particles and increasing vulnerability to LDL oxidation

Promoter polymorphism that modulates PON1 gene expression level — the G allele (plus-strand alternate; corresponds to coding-strand C at the -909 position) reduces transcriptional output, lowering circulating PON1 enzyme and diminishing HDL-associated antioxidant protection against LDL oxidation.

Promoter variant in UGT1A1 that tags the *28 reduced-expression haplotype; T allele carriers have lower hepatic UGT1A1 expression, mildly elevated unconjugated bilirubin (Gilbert syndrome spectrum), and altered metabolism of bilirubin, atazanavir, and irinotecan

Regulatory tag variant near SOX17 at chromosome 8q11.23 associated with intracranial aneurysm susceptibility in European and East Asian populations; A allele confers elevated risk through putative effects on SOX17 endothelial transcription factor expression