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Table 4 Methylation difference of HTRA1 between stroke cases and controls stratified by age in the prospective nested 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 (88 stroke cases vs. 90 controls)

        

HTRA1_A_CpG_1

0.07 (0.05–0.10)

0.07 (0.05–0.09)

0.72 (0.33–1.61)

0.427

0.72 (0.33–1.61)

0.428

0.67 (0.30–1.54)

0.348

HTRA1_A_CpG_2

0.78 (0.74–0.84)

0.77 (0.73–0.82)

1.09 (0.85–1.40)

0.504

1.08 (0.84–1.39)

0.542

1.15 (0.88–1.50)

0.316

HTRA1_A_CpG_3

0.44 (0.41–0.51)

0.46 (0.41–0.52)

1.02 (0.75–1.39)

0.899

1.05 (0.76–1.44)

0.772

1.05 (0.75–1.46)

0.780

HTRA1_A_CpG_4

0.19 (0.16–0.21)

0.20 (0.17–0.22)

1.39 (0.65–2.99)

0.400

1.38 (0.63–2.99)

0.421

1.54 (0.69–3.43)

0.295

HTRA1_A_CpG_5

0.41 (0.35–0.49)

0.41 (0.35–0.46)

0.89 (0.67–1.17)

0.394

0.88 (0.66–1.16)

0.365

0.87 (0.65–1.16)

0.339

HTRA1_A_CpG_6

0.09 (0.08–0.11)

0.08 (0.07–0.10)

0.59 (0.30–1.18)

0.135

0.57 (0.28–1.14)

0.110

0.55 (0.27–1.12)

0.101

HTRA1_A_CpG_7

0.39 (0.34–0.45)

0.40 (0.35–0.45)

1.20 (0.82–1.76)

0.343

1.23 (0.84–1.81)

0.297

1.22 (0.82–1.81)

0.320

HTRA1_B_CpG_1

0.19 (0.11–0.29)

0.18 (0.11–0.30)

1.11 (0.91–1.36)

0.299

1.11 (0.91–1.36)

0.322

1.14 (0.93–1.41)

0.208

HTRA1_B_CpG_2

0.12 (0.09–0.16)

0.13 (0.08–0.17)

1.17 (0.69–2.01)

0.560

1.19 (0.69–2.04)

0.534

1.19 (0.69–2.07)

0.528

HTRA1_B_CpG_3.4

0.31 (0.26–0.35)

0.33 (0.27–0.37)

1.23 (0.85–1.79)

0.278

1.21 (0.83–1.77)

0.321

1.22 (0.83–1.79)

0.312

HTRA1_B_CpG_5

0.34 (0.28–0.40)

0.34 (0.26–0.43)

1.06 (0.80–1.41)

0.688

1.05 (0.79–1.39)

0.751

1.04 (0.78–1.40)

0.781

HTRA1_B_CpG_7

0.47 (0.39–0.53)

0.46 (0.38–0.58)

1.04 (0.83–1.32)

0.720

1.03 (0.81–1.30)

0.826

1.03 (0.80–1.31)

0.833

HTRA1_B_CpG_8.9

0.31 (0.26–0.35)

0.33 (0.27–0.37)

1.23 (0.85–1.79)

0.278

1.21 (0.83–1.77)

0.321

1.22 (0.83–1.79)

0.312

HTRA1_B_CpG_10

0.61 (0.55–0.69)

0.66 (0.56–0.75)

1.17 (0.91–1.51)

0.233

1.17 (0.90–1.51)

0.236

1.18 (0.90–1.54)

0.224

HTRA1_B_CpG_11.12

0.75 (0.69–0.79)

0.75 (0.70–0.82)

1.14 (0.83–1.58)

0.428

1.12 (0.81–1.55)

0.509

1.11 (0.79–1.55)

0.558

HTRA1_B_CpG_13.14.15

0.54 (0.46–0.61)

0.56 (0.47–0.61)

1.17 (0.88–1.54)

0.281

1.15 (0.87–1.53)

0.314

1.16 (0.87–1.54)

0.317

HTRA1_B_CpG_16

0.48 (0.42–0.58)

0.49 (0.37–0.57)

0.92 (0.76–1.12)

0.393

0.91 (0.75–1.11)

0.351

0.90 (0.74–1.10)

0.321

Participants ≥ 70 years old (51 stroke cases vs. 53 controls)

        

HTRA1_A_CpG_1

0.07 (0.06–0.08)

0.07 (0.05–0.09)

0.73 (0.25–2.13)

0.563

0.66 (0.22–1.98)

0.457

0.67 (0.20–2.22)

0.511

HTRA1_A_CpG_2

0.76 (0.71–0.82)

0.76 (0.71–0.81)

0.86 (0.65–1.14)

0.303

0.87 (0.65–1.16)

0.330

0.86 (0.60–1.23)

0.418

HTRA1_A_CpG_3

0.44 (0.38–0.47)

0.46 (0.42–0.54)

1.78 (1.08–2.93)

0.024

1.77 (1.06–2.93)

0.028

1.69 (0.97–2.93)

0.063

HTRA1_A_CpG_4

0.20 (0.17–0.22)

0.19 (0.17–0.21)

1.02 (0.50–2.09)

0.962

1.01 (0.49–2.10)

0.975

0.90 (0.40–2.02)

0.803

HTRA1_A_CpG_5

0.44 (0.38–0.51)

0.40 (0.34–0.45)

0.71 (0.50–1.01)

0.054

0.72 (0.50–1.02)

0.065

0.62 (0.40–1.01)

0.053

HTRA1_A_CpG_6

0.09 (0.08–0.10)

0.08 (0.07–0.10)

0.94 (0.35–2.48)

0.895

1.02 (0.38–2.74)

0.973

0.99 (0.33–2.96)

0.988

HTRA1_A_CpG_7

0.39 (0.35–0.42)

0.40 (0.34–0.48)

1.10 (0.69–1.75)

0.688

1.06 (0.66–1.71)

0.806

0.91 (0.54–1.52)

0.711

HTRA1_B_CpG_1

0.17 (0.12–0.25)

0.18 (0.10–0.29)

1.08 (0.85–1.36)

0.530

1.06 (0.84–1.35)

0.621

0.98 (0.75–1.28)

0.900

HTRA1_B_CpG_2

0.13 (0.09–0.17)

0.11 (0.08–0.16)

0.94 (0.52–1.69)

0.832

0.98 (0.54–1.77)

0.936

1.18 (0.60–2.31)

0.636

HTRA1_B_CpG_3.4

0.30 (0.25–0.35)

0.32 (0.27–0.37)

1.72 (0.97–3.06)

0.064

1.73 (0.97–3.08)

0.064

2.36 (1.18–4.73)

0.015

HTRA1_B_CpG_5

0.31 (0.26–0.39)

0.38 (0.28–0.47)

1.50 (1.03–2.19)

0.033

1.59 (1.07–2.37)

0.023

1.70 (1.08–2.67)

0.021

HTRA1_B_CpG_7

0.49 (0.40–0.53)

0.48 (0.41–0.57)

1.10 (0.82–1.48)

0.540

1.09 (0.81–1.47)

0.583

1.09 (0.78–1.52)

0.614

HTRA1_B_CpG_8.9

0.30 (0.25–0.35)

0.32 (0.27–0.37)

1.72 (0.97–3.06)

0.064

1.73 (0.97–3.08)

0.064

2.36 (1.18–4.73)

0.015

HTRA1_B_CpG_10

0.64 (0.54–0.69)

0.68 (0.53–0.76)

1.14 (0.87–1.49)

0.333

1.14 (0.87–1.49)

0.338

1.23 (0.91–1.65)

0.178

HTRA1_B_CpG_11.12

0.73 (0.68–0.78)

0.77 (0.68–0.83)

1.54 (1.01–2.35)

0.043

1.49 (0.98–2.28)

0.064

1.35 (0.85–2.15)

0.203

HTRA1_B_CpG_13.14.15

0.53 (0.47–0.57)

0.57 (0.50–0.67)

1.76 (1.16–2.69)

0.008

1.78 (1.15–2.76)

0.009

1.76 (1.09–2.86)

0.021

HTRA1_B_CpG_16

0.47 (0.39–0.55)

0.49 (0.37–0.60)

1.02 (0.79–1.30)

0.901

1.03 (0.80–1.32)

0.837

1.04 (0.79–1.37)

0.763

  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