LINE-1 Hypomethylation is Associated with the Risk of Coronary Heart Disease in Chinese Population

Abstract

BackgroundGlobal methylation level in blood leukocyte DNA has been associated with the risk of coronary heart disease (CHD), with inconsistent results in various populations. Similar data are lacking in Chinese population where different genetic, lifestyle and environmental factors may affect DNA methylation and its risk relationship with CHD.ObjectivesTo examine whether global methylation is associated with the risk of CHD in Chinese population.MethodsA total of 334 cases with CHD and 788 healthy controls were included. Global methylation in blood leukocyte DNA was estimated by analyzing LINE-1 repeats using bisulfite pyrosequencing.ResultsIn an initial analysis restricted to control subjects, LINE-1 level reduced significantly with aging, elevated total cholesterol, and diagnosis of diabetes. In the case-control analysis, reduced LINE-1 methylation was associated with increased risk of CHD; analysis by quartile revealed odds ratios (95%CI) of 0.9 (0.6-1.4), 1.9 (1.3-2.9) and 2.3 (1.6-3.5) for the third, second and first (lowest) quartile (Ptrend < 0.001), respectively, compared to the fourth (highest) quartile. Lower (<median) LINE-1 methylation was associated with a 2.2-fold (95%CI = 1.7-3.0) increased risk of CHD. The lower LINE-1-related CHD risk estimates tended to be stronger among subjects with the highest tertile of homocysteine (Pinteraction = 0.042) and those with diagnosis of hypertension (Pinteraction = 0.012).ConclusionLINE-1 hypomethylation is associated with the risk of CHD in Chinese population. Potential CHD risk factors such as older age, elevated total cholesterol, and diagnosis of diabetes may have impact on global DNA methylation, whereby exerting their effect on CHD risk.

Association between DNA methylation and coronary heart disease or other atherosclerotic events: A systematic review

“…In total, 51 articles met our eligibility criteria (Supplementary Table 1) and were included in the analysis. Of the 51 selected studies, 17 included participants from Europe [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] 14 from China [23][24][25][26][27][28][29][30][31][32][33][34][35][36], six from USA [37][38][39][40][41][42], three from India [43][44][45], two from Canada [46,47], and one each from Japan [48], Malaysia [49], Iran [50], Russia [51], Brazil [52] and Mexico [53]…”

“…Seven studies analyzed global DNA methylation [6,7,23,34,36,42,52], 31 followed a candidate-gene approach [8][9][10][11][12][13][14]20,22,[24][25][26][27][28][29][30][31][32][33]35,[38][39][40][41]45,46,49,50,[54][55][56], seven were epigenome-wide association studies (EWAS) [16,18,19,21,44,48,53], two used both global DNA methylation and candidate-gene approaches [37,43], three used EWAS and global DNA methylation approaches [15,17,51], and on...…”

Lack of an association between matrix metalloproteinase polymorphisms and coronary heart disease in a Han Chinese population

“…Epigenetic marks such as DNA methylation of cytosine residues in CpG dinucleotides have been shown to be helpful in the advance diagnosis of CHD (Wei et al, 2014). SNPs rs3918250 and rs2075847 are promoter CpG polymorphisms and might therefore affect gene expression, although evidence is needed to support this hypothesis.…”

Serine hydroxymethyltransferase 1 promoter hypermethylation increases the risk of essential hypertension

“…Participants older than 65 years had a 1.46‐fold increased risk of higher SHMT1 promoter methylation. Consistent with our study, previous studies also indicated a positive association between increased DNA promoter methylation, such as that for ADD1 and LINE‐1 , and older age. Changes in DNA methylation may be induced by aging and environmental exposures …”