title: Homocysteine diminishes apolipoprotein A-I function and expression in patients with hypothyroidism: a cross-sectional study.
abstract: BACKGROUND
  Hypothyroidism (HO) can significantly impair lipid metabolism and increase cardiovascular disease risk. Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease. Our previous study demonstrated that HHcy significantly induced insulin resistance and impaired coronary artery endothelial function in patients with either hypertension or HO. In the present study, we studied whether plasma levels of high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-I (Apo A-I) were altered in patients with HO, and if so, whether this change was mediated by HHcy.
  
  
  METHODS
  A total of 258 subjects were enrolled and divided into the following three groups: control group (n = 94), HO group (n = 73), and subclinical hypothyroidism (SHO) group (n = 91). Additionally, all groups were subdivided based on the subjects' Hcy levels into HHcy (plasma Hcy level over 15 μmol/l) and normal Hcy subgroups. The plasma levels of lipid indexes were measured. Statistical analyses were performed to evaluate the correlations between groups.
  
  
  RESULTS
  The plasma Hcy levels were significantly higher in the HO group than in the SHO or control groups (all p < 0.05). Moreover, levels of Apo A-I and HDL-C were markedly reduced in the HHcy subgroup compared with the normal Hcy subgroup for patients with either HO (Apo A-I: p < 0.05; HDL-C: p < 0.01) or SHO (Apo A-I: p < 0.05; HDL-C: p < 0.01). In addition, the plasma Hcy levels were negatively correlated with levels of Apo A-I in all three groups (HO group: r = - 0.320, SHO group: r = - 0.337 and control group: r = - 0.317; all p < 0.01).
  
  
  CONCLUSIONS
  Hcy levels were significantly increased in patients with HO or SHO. These increased Hcy levels may impair cardiovascular function via the inhibition of Apo A-1 expression and impairment of its antioxidant capacity. Our findings provide new insights into the pathogenesis of hypothyroidism-induced metabolic disorders.
authors.affiliation: Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang district, Beijing, 100020, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang district, Beijing, 100020, People's Republic of China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang district, Beijing, 100020, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Miao
authors.affiliation: Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang district, Beijing, 100020, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang district, Beijing, 100020, People's Republic of China.
authors.forename: Xia
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang district, Beijing, 100020, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang district, Beijing, 100020, People's Republic of China. drwg6688@sina.com.
authors.forename: Guang
authors.initials: G
authors.lastname: Wang
mesh_terms: D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood* / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D015870:Gene Expression; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D007037:Hypothyroidism / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D006710:Homocysteine
keywords: Apolipoprotein A-I; High-density lipoprotein-cholesterol; Homocysteine; Hypothyroidism