Polymorphisms of the Flavin containing monooxygenase 3 (FMO3) gene do not predispose to essential hypertension in Caucasians

Abstract

BackgroundThe recessive disorder trimethylaminuria is caused by defects in the FMO3 gene, and may be associated with hypertension. We investigated whether common polymorphisms of the FMO3 gene confer an increased risk for elevated blood pressure and/or essential hypertension.MethodsFMO3 genotypes (E158K, V257M, E308G) were determined in 387 healthy subjects with ambulatory systolic and diastolic blood pressure measurements, and in a cardiovascular disease population of 1649 individuals, 691(41.9%) of whom had a history of hypertension requiring drug treatment. Haplotypes were determined and their distribution noted.ResultsThere was no statistically significant association found between any of the 4 common haplotypes and daytime systolic blood pressure in the healthy population (p = 0.65). Neither was a statistically significant association found between the 4 common haplotypes and hypertension status among the cardiovascular disease patients (p = 0.80).ConclusionThese results suggest that the variants in the FMO3 gene do not predispose to essential hypertension in this population.

Genetic Polymorphisms of Human Flavin-Containing Monooxygenase 3: Implications for Drug Metabolism and Clinical Perspectives

“…For example, certain FMO3 polymorphisms are not associated with common diseases such as colorectal cancer and hypertension [68,69]. This is one gray area illustrative of the amount of additional research needed to establish the significance of FMO3 polymorphisms in human diseases and their management.…”

Association of moderately elevated trimethylamine N-oxide with cardiovascular risk: is TMAO serving as a marker for hepatic insulin resistance

“…This raises the interesting prospect that drugs selectively targeting FMO3 might have some utility in diabetes and hyperlipidaemia, particularly when elevated TMAO levels suggest that hepatic FMO3 expression is high. However, since FMO3 plays a systemic role in catecholamine metabolism, suppressing its function might not prove to be innocuous; genetic absence of FMO3 activity has been associated with hypertension 147. In any case, when hepatic insulin resistance is present, correcting this should lessen hepatic FMO3 expression.…”

Flavin-containing monooxygenases in aging and disease: Emerging roles for ancient enzymes

“…The proposed mechanism was that FMO3 could metabolize tyramine, an endogenous pressor molecule, thereby reducing its pressor effects and lowering blood pressure (43). A follow-up study found that none of three examined FMO3 polymorphisms predispose to hypertension in a sample of several hundred Caucasian patients, but also noted that severe, highly penetrant loss-of-function mutations could "unmask pressor effects of variation in other drug metabolizing enzymes previously buffered by FMO3" (51). At least two more recent studies are consistent with TMAO production having a reactive, protective function in response to CVD pathology (52,53), with one of these studies asserting that TMAO is, in fact, protective against CVD risk (53).…”