reactive oxygen species, and inflammation lead to fat cell dysfunction (also see 12-HETE#Inflammation and inflammatory diseases and 12-HETE#Diabetes). Indeed, in one study a Single-nucleotide polymorphism, rs2073438, located in an intron region of the ALOX12 gene was significantly associated with total and percentage fat mass of obese compared to non-obese young Chinese men. ALOX12 and 12(S)-HETE are likewise implicated in essential hypertension (see next section). Hence, ALOX12 and its metabolite(s) may contribute to the development and/or progression of obesity, diabetes, hypertension, and/or the metabolic syndrome. Blood vessels A selective but not totally specific inhibitor of ALOX12 reduced the growth response of cultured human endothelial cells to basic fibroblast growth factor and vascular endothelial growth factor (VEGF); this reduction was partially reversed by 12(S)-HETE; 12(S)-HETE also stimulates human prostate cell lines to produce VEGF. These results suggest that growth responses to the two growth factors involves their stimulation of 12(S)-HETE production by endothelial cells and therefore that ALOX12 may be a target for reducing the neo-vascularization that promotes arthritic and cancer diseases. 12(S)-HETE also dilates human coronary microcirculation arteries by activating these vessels' smooth muscle BKca Potassium channels and is therefore suggested to be an Endothelium-derived hyperpolarizing factor. Finally, a single nucleotide variant in the ALOX12 gene (R261Q [3957 G>A]) has been associated with essential hypertension and elevation in the urinary excretion of 12(S)-HETE in humans and may be a contributing factor for to essential hypertension (see also 12-HETE#Blood pressure). Alzheimer's disease Patients with Alzheimer's disease or other forms of dementia have significantly higher levels of 12(S)-HETE (and 15(S)-HETE) in cerebrospinal fluid compared to aged-matched normal individuals. Complementary studies in rodent models bearing human mutated genes for Amyloid precursor protein and/or tau protein (see tau protein#Clinical significance) that produce Alzheimer's dementia-like syndromes implicate 12(S)-HETE, 15(S)-HETE, and a 12/15-lipoxygenase type enzyme in the development and progression of the Alzhiemer's disease-like symptoms and findings in these animals. In a single study, ALOX12 mRNA was found elevated in the brain tissue of Alzheimer disease patients compared to control patients. These results suggest that ALOX12 (or ALOX15) may contribute to the development of Alzheimer's disease in humans. Cancer Studies in prostate cancer find that human prostate cancer cell lines in culture overexpress ALOX12, overproduce 12(S)-HETE, and respond to 12(S)-HETE by increasing their rate of proliferation, increasing their cell surface expression of integrins, increasing their survival and delaying their apoptosis, and increasing their production of vascular endothelial