Homocysteine and MTHFR Gene Polymorphism in Patients with Obstructive Sleep Apnea

Abstract

Obstructive sleep apnea (OSA) is characterized by repetitive obstruction of upper airway, leading to repeated arterial oxygen desaturation. The prevalence of cardiovascular disease, including arterial hypertension, myocardial infarction, atherosclerosis and stroke is increased among patients with OSA. Although exact mechanism for this reason is not understood, it is postulated that hypoxic stress induced by OSA may be involved in the etiology of cardiovascular disorder. Homocysteine (Hey), which has been reported as independent risk factors for vascular disease in many studies, is a sulfur-containing amino acid formed during the metabolism of methionine. Therefore, we hypothesized that OSA induced hypoxic stress might be correlated with oxidative stress, we investigated association between homocysteine and MTHFR gene mutation in OSA patients. Levels of homocysteine, cholesterol, low-density lipoprotein, high-density lipoprotein, try glycerides, creatinine, vitamin B 12 and folic acid were determined in 82 participants after overnight fasting. All subjects underwent computerized portable polysomnogram (PSG) in the home. Among these study participants, inclusion criteria were Apnea Hypopnea Index (AHI)>20 for moderate to severe OSA (Group A), 5≤AHI≤20 for mild OSA subjects (Group B) and AHI<5 for control subjects (Group C) matched by age. Moderate to severe OSA patients has significantly higher homocysteine levels (14.72.7 umol/L, P<0.001) than other groups. MTHFR (C677T) gene polymorphism did not differ between patients and control. Homocysteine level showed positive correlation with square root transformed AHI (r=0.663, P<0.001). Also, AHI and MTHFR gene mutation (T677T) have an independent effect on homocysteine levels in multiple regression models. Severe OSA is an independent effect on elevated homocysteine levels. We hypothesize that these results may be explained by endothelial dysfunction combined with excess free-radical formation in OSA patients. Further study will be warranted to elucidate the relationship between hypoxic stress and homocysteine levels in OSA patients.