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Table 3 Methylation difference of HTRA1 between stroke cases and controls stratified by age in the case–control study

From: HTRA1 methylation in peripheral blood as a potential marker for the preclinical detection of stroke: a case–control study and a prospective nested case–control study

CpG sites

Controls

Stroke cases

Crude OR (95% CI)

P value

OR (95% CI)

P value

OR (95% CI)*

P value*

Median (IQR)

Median (IQR)

Per + 10% methylation

Per + 10% methylation

Per + 10% methylation

Participants < 70 years old (116 stroke cases vs. 125 controls)

        

HTRA1_A_CpG_1

0.09 (0.05–0.13)

0.11 (0.08–0.13)

1.23 (0.84–1.81)

0.293

1.23 (0.84–1.81)

0.293

1.20 (0.76–1.89)

0.448

HTRA1_A_CpG_2

0.65 (0.57–0.79)

0.64 (0.56–0.74)

0.98 (0.86–1.11)

0.707

0.98 (0.86–1.11)

0.696

0.96 (0.83–1.10)

0.510

HTRA1_A_CpG_3

0.28 (0.22–0.35)

0.30 (0.25–0.35)

1.10 (0.85–1.41)

0.484

1.10 (0.85–1.41)

0.489

1.13 (0.85–1.51)

0.409

HTRA1_A_CpG_4

0.12 (0.09–0.15)

0.13 (0.11–0.15)

1.31 (0.74–2.30)

0.354

1.30 (0.74–2.29)

0.369

1.02 (0.54–1.94)

0.951

HTRA1_A_CpG_5

0.37 (0.31–0.43)

0.38 (0.30–0.43)

0.96 (0.81–1.15)

0.679

0.96 (0.81–1.15)

0.680

0.97 (0.79–1.18)

0.731

HTRA1_A_CpG_6

0.12 (0.10–0.14)

0.10 (0.06–0.14)

0.66 (0.40–1.08)

0.097

0.66 (0.40–1.09)

0.106

0.69 (0.41–1.16)

0.163

HTRA1_A_CpG_7

0.36 (0.28–0.45)

0.37 (0.31–0.45)

1.04 (0.86–1.27)

0.685

1.04 (0.85–1.27)

0.713

1.06 (0.85–1.34)

0.602

HTRA1_B_CpG_1

0.16 (0.09–0.40)

0.18 (0.11–0.50)

1.09 (0.98–1.21)

0.122

1.09 (0.98–1.22)

0.123

1.11 (0.98–1.25)

0.107

HTRA1_B_CpG_2

0.09 (0.05–0.12)

0.11 (0.07–0.15)

1.66 (0.93–3.03)

0.102

1.65 (0.92–3.01)

0.103

1.80 (0.96–3.23)

0.062

HTRA1_B_CpG_3.4

0.28 (0.23–0.32)

0.29 (0.25–0.34)

1.41 (0.97–2.03)

0.069

1.42 (0.98–2.05)

0.063

1.29 (0.85–1.96)

0.230

HTRA1_B_CpG_5

0.25 (0.19–0.33)

0.28 (0.22–0.33)

1.19 (0.92–1.54)

0.190

1.20 (0.93–1.56)

0.169

1.18 (0.88–1.58)

0.274

HTRA1_B_CpG_7

0.47 (0.35–0.54)

0.46 (0.38–0.53)

1.07 (0.88–1.29)

0.520

1.06 (0.88–1.29)

0.535

0.99 (0.79–1.23)

0.906

HTRA1_B_CpG_8.9

0.28 (0.23–0.32)

0.29 (0.25–0.34)

1.41 (0.97–2.03)

0.069

1.42 (0.98–2.05)

0.063

1.29 (0.85–1.96)

0.230

HTRA1_B_CpG_10

0.61 (0.53–0.71)

0.64 (0.55–0.70)

1.14 (0.94–1.38)

0.180

1.14 (0.94–1.38)

0.173

1.13 (0.92–1.40)

0.249

HTRA1_B_CpG_11.12

0.72 (0.64–0.79)

0.73 (0.67–0.80)

1.13 (0.89–1.43)

0.330

1.12 (0.89–1.42)

0.343

1.11 (0.85–1.45)

0.451

HTRA1_B_CpG_13.14.15

0.48 (0.40–0.56)

0.50 (0.45–0.57)

1.24 (0.99–1.55)

0.066

1.24 (0.99–1.55)

0.068

1.19 (0.92–1.55)

0.186

HTRA1_B_CpG_16

0.51 (0.43–0.62)

0.53 (0.44–0.66)

1.08 (0.92–1.27)

0.367

1.08 (0.92–1.28)

0.356

1.03 (0.85–1.24)

0.800

Participants ≥ 70 years old (74 stroke cases vs. 65 controls)

        

HTRA1_A_CpG_1

0.09 (0.06–0.12)

0.10 (0.07–0.14)

1.38 (0.77–2.45)

0.278

1.37 (0.77–2.44)

0.282

1.43 (0.73–2.82)

0.300

HTRA1_A_CpG_2

0.63 (0.56–0.71)

0.65 (0.59–0.78)

1.08 (0.92–1.27)

0.335

1.09 (0.92–1.28)

0.340

1.05 (0.85–1.30)

0.631

HTRA1_A_CpG_3

0.32 (0.25–0.38)

0.28 (0.22–0.36)

0.76 (0.54–1.05)

0.097

0.74 (0.53–1.04)

0.087

0.63 (0.42–0.94)

0.022

HTRA1_A_CpG_4

0.12 (0.09–0.15)

0.12 (0.11–0.15)

1.79 (0.87–3.71)

0.116

1.80 (0.87–3.74)

0.113

1.92 (0.78–4.70)

0.156

HTRA1_A_CpG_5

0.37 (0.3–0.46)

0.38 (0.29–0.49)

1.04 (0.82–1.32)

0.750

1.04 (0.82–1.32)

0.752

1.01 (0.76–1.33)

0.967

HTRA1_A_CpG_6

0.12 (0.10–0.15)

0.10 (0.07–0.13)

0.27 (0.12–0.63)

0.003

0.27 (0.11–0.62)

0.002

0.29 (0.12–0.73)

0.008

HTRA1_A_CpG_7

0.36 (0.27–0.46)

0.38 (0.30–0.48)

1.16 (0.88–1.53)

0.282

1.15 (0.88–1.52)

0.310

1.12 (0.81–1.53)

0.497

HTRA1_B_CpG_1

0.15 (0.09–0.42)

0.17 (0.09–0.42)

0.96 (0.83–1.10)

0.557

0.95 (0.83–1.10)

0.529

0.94 (0.79–1.13)

0.511

HTRA1_B_CpG_2

0.08 (0.05–0.14)

0.09 (0.07–0.12)

0.92 (0.56–1.52)

0.756

0.92 (0.56–1.52)

0.749

0.70 (0.39–1.28)

0.251

HTRA1_B_CpG_3.4

0.30 (0.25–0.34)

0.29 (0.23–0.34)

0.92 (0.60–1.41)

0.701

0.93 (0.60–1.44)

0.737

0.85 (0.50–1.43)

0.534

HTRA1_B_CpG_5

0.27 (0.22–0.36)

0.28 (0.21–0.34)

0.96 (0.71–1.30)

0.779

0.97 (0.71–1.32)

0.822

0.87 (0.60–1.26)

0.455

HTRA1_B_CpG_7

0.48 (0.38–0.55)

0.49 (0.34–0.56)

1.04 (0.84–1.29)

0.731

1.05 (0.84–1.32)

0.650

1.00 (0.75–1.33)

0.999

HTRA1_B_CpG_8.9

0.30 (0.25–0.34)

0.29 (0.23–0.34)

0.92 (0.60–1.41)

0.701

0.93 (0.60–1.44)

0.737

0.85 (0.50–1.43)

0.534

HTRA1_B_CpG_10

0.63 (0.55–0.73)

0.62 (0.53–0.72)

0.94 (0.74–1.19)

0.615

0.94 (0.74–1.20)

0.619

0.78 (0.57–1.07)

0.117

HTRA1_B_CpG_11.12

0.72 (0.66–0.82)

0.72 (0.65–0.82)

1.06 (0.81–1.37)

0.685

1.06 (0.81–1.39)

0.669

0.96 (0.67–1.37)

0.815

HTRA1_B_CpG_13.14.15

0.51 (0.42–0.62)

0.51 (0.44–0.57)

1.02 (0.79–1.32)

0.863

1.03 (0.79–1.34)

0.819

0.98 (0.70–1.38)

0.914

HTRA1_B_CpG_16

0.55 (0.47–0.67)

0.53 (0.45–0.69)

0.95 (0.78–1.17)

0.642

0.96 (0.78–1.17)

0.659

0.92 (0.72–1.17)

0.496

  1. Bold values indicated P < 0.05
  2. logistic regression, adjusted for age and sex
  3. *logistic regression, adjusted for age, sex, smoking, drinking, hypertension, diabetes, TC, TG, HDL-C and LDL-C