Abstract
BackgroundDyslipidemia is a well-established risk factor for cardiovascular disease. Serum lipids were affected by several gene polymorphisms, folate, homocysteine and other metabolite levels. We aim to investigate the effects of homocysteine metabolism enzyme polymorphisms (MTHTR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) and their interactions with folate, homocysteine on serum lipid levels in Chinese patients with hypertension.MethodsParticipants were 480 hypertensive adults that enrolled in September to December 2005 from six different Chinese hospitals (Harbin, Shanghai, Shenyang, Beijing, Xi’an, and Nanjing). Known MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G genotypes were determined by PCR-RFLP methods. Serum folate was measured by chemiluminescent immunoassay, homocysteine was measured by high-performance liquid chromatography, serum lipids parameters were determined by an automatic biochemistry analyzer, low-density lipoprotein was calculated by Friedewald’s equation. Unitary linear regression model was used to assess the associations of gene polymorphisms, folate and homocysteine on serum lipid profiles. Unconditional logistic regression model was applied to test the interactions of folate, homocysteine and gene polymorphisms on dyslipidemia.ResultsNo correlations between gene polymorphisms and homocysteine on serum lipid profiles. Compared with normal folate patients, patients with low folate showed higher odds of hypertriglyceridemia (OR = 2.02, 95 % CI: 1.25-3.25, P = 0.004) and low levels of high-density lipoprotein cholesterol (OR = 1.88, 95 % CI: 1.07-3.28, P = 0.027). Each of four gene polymorphisms (MTHTR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) combined with low folate showed higher odds of hypertriglyceridemia (P for trend: 0.049, 0.004, 0.007 and 0.005, respectively). MTHFR C677T and A1298C with low folate showed higher odds of low levels of high-density lipoprotein cholesterol (P for trend: 0.008 and 0.031).ConclusionsLow folate status and homocysteine metabolism gene polymorphisms (MTHTR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) may have a synergistic effect increased the incidence of dyslipidemia in Chinese hypertensive population.
Highlights
Dyslipidemia is a well-established risk factor for cardiovascular disease
We aim to explore the independent associations of folate, Hcy and these four gene polymorphisms (MTHFR C677T, methylenetetrahydrofolate reductase (MTHFR) A1298C, Methionine synthase (MTR) A2756G and Methionine synthase reductase (MTRR) A66G) on serum lipid profiles, as well as to evaluate the joint effect of gene, Hcy and genotypes on dyslipidemia in Chinese hypertensive patients
Four gene polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) in this population had no deviation from the Hardy-Weinberg equilibrium (P values were 0.885, 0.384, 0.937 and 0.400, respectively)
Summary
Dyslipidemia is a well-established risk factor for cardiovascular disease. We aim to investigate the effects of homocysteine metabolism enzyme polymorphisms (MTHTR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) and their interactions with folate, homocysteine on serum lipid levels in Chinese patients with hypertension. Cardiovascular diseases (CVDs) are still a major cause of morbidity and mortality worldwide, which is expected to remain the same during the foreseeable future [1]. Dyslipidemia is a major risk factor for stroke, coronary artery disease, atherosclerosis and other CVDs [2,3,4]. Abnormal folate or homocysteine (Hcy) level was exacerbated the incidence of CVDs [9, 10]. A large sample of clinical trials showed folate supplements effectively lower Hcy level and reduced the risk of stroke [11]. The potential mechanisms of folate, Hcy and serum lipid levels remain to be explored
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