Table 1 Clinical features of individuals included in the study cohorts stratified by sex

From: Interaction between estrogen receptor-α and PNPLA3 p.I148M variant drives fatty liver disease susceptibility in women

 

Liver biopsy cohort (n = 1,861)

Women (n = 920, 49.4%)

Men (n = 941, 50.6%)

P value

Age (years)

45.1 ± 14.0

42.9 ± 16.0

0.002

Menopause (no/transition/yes)a

379/273/268 (41.2/29.7/29.1)

N/A

N/A

BMI (kg m−2)

38.1 ± 8.7

31.6 ± 8.0

<0.0001

Severe obesity

406 (43.8)

156 (16.6)

<0.0001

T2D/IFG (yes)

225 (24.5)

258 (27.7)

0.16

Total cholesterol (mg dl−1)

192 ± 46

190 ± 42

0.89

Triglycerides (mg dl−1)

130 ± 64

146 ± 84

<0.0001

HDL-cholesterol (mg dl−1)

52 ± 16

44 ± 11

<0.0001

ALT (IU l−1)

54 (34-80)

30 (19-48)

<0.0001

AST (IU l−1)

34 (24-47)

22 (17-33)

<0.0001

NASH (yes)

249 (27.1)

370 (39.4)

<0.0001

Clinically significant fibrosis (yes)

161 (17.5)

259 (27.6)

<0.0001

PNPLA3, p.148M/M

128 (13.9)

142 (15.1)

0.51

 

Transcriptomic cohort (n = 125)

Women (n = 107, 85.6%)

Men (n = 18, 14.4%)

P value

Age (years)

43.9 ± 10.5

42.5 ± 10.7

0.61

Menopause (no/transition/yes)b

55/35/17 (51.4/32.7/15.9)

N/A

N/A

BMI (kg m−2)

40.4 ± 7.4

42.3 ± 6.4

0.29

T2D/IFG (yes)

13 (12.2)

2 (11.1)

0.87

Total cholesterol (mg dl−1)

208 ± 47

214 ± 43

0.71

Triglycerides (mg dl−1)

132 ± 59

132 ± 59

0.48

HDL-cholesterol (mg dl−1)

56 ± 14

46 ± 9

0.031

ALT (IU l−1)

19 (14-26)

39 (24-51)

0.025

AST (IU l−1)

17 (15-20)

26 (17-31)

0.37

NASH (yes)

8 (7.5)

6 (33.3)

0.001

Clinically significant fibrosis (yes)

4 (3.7)

3 (16.7)

0.20

PNPLA3, p.148M/M

8 (7.5)

1 (5.6)

0.08

 

Severe FLD case–control cohort (n = 4,374)

Women (n = 1,383, 31.6%)

Men (n = 2,991, 68.4%)

P value

Age (years)

44.2 ± 15.4

47.3 ± 13.8

<0.0001

Menopause (no/transition/yes)c

1,089/897/1,006 (36.4/30.0/33.6)

NA

NA

Advanced fibrosis (yes)

168 (12.1)

343 (11.5)

0.51

HCC (yes)

38 (2.8)

133 (4.4)

0.007

PNPLA3, p.148M/M

171 (12.4)

1303 (10.1)

0.028

 

Liver-Bible-2022 cohort (n = 1142)

Women (n = 191, 16.7%)

Men (n = 951, 83.3%)

P value

Age (years)

53.9 ± 5.9

53.9 ± 6.5

0.98

Menopause (no/transition/yes)d

69/10/112 (36.1/5.2/58.7)

N/A

N/A

BMI (kg m−2)

28.8 ± 3.7

28.5 ± 3.0

0.26

T2D/IFG (yes)

26 (13.6)

56 (5.9)

0.0006

Total cholesterol (mg dl−1)

208 ± 34

202 ± 33

0.034

Triglycerides (g dl−1)

147 ± 62

166 ± 86

0.0006

HDL-cholesterol (mg dl−1)

52 ± 10

44 ± 9

<0.0001

ALT (IU l−1)

21 (16–27)

28 (22–37)

<0.0001

AST (IU l−1)

20 (17–23)

23 (20–27)

<0.0001

NAFLD (controlled attenuation parameter ≥ 275 dB m−1)

80 (41.9)

469 (49.5)

0.057

Clinically significant fibrosis (LSM ≥ 8 kPa)

1 (0.5)

25 (2.6)

0.11

PNPLA3, p.148M/M

17 (8.9)

75 (7.9)

0.31

 

cfDNA from patients of Liver-Bible-2022 cohort (n = 91)

Women (n = 6, 6.6%)

Men (n = 85, 93.4%)

P value

Age (years)

53.8 ± 6.8

53.4 ± 6.8

0.91

Menopause (yes)

4 (66.7)

N/A

N/A

 

UK Biobank cohort (n = 347,127)

Women (n = 186,625, 53.8%)

Men (n = 160,502, 42.2%)

P value

Age (years)

56.6 ± 7.9

57.0 ± 8.1

<0.0001

Menopause (yes)

134,358 (72.0)

N/A

N/A

E2 (pmol l−1)

538 ± 476

228 ± 79

<0.0001

BMI (kg m−2)

27.0 ± 5.1

27.8 ± 4.2

<0.0001

T2D (yes)

12,567 (6.7)

19,300 (12.0)

<0.0001

Total cholesterol (mg dl−1)

228 ± 43

213 ± 43

<0.0001

Triglycerides (g dl−1)

137 ± 75

175 ± 100

<0.0001

HDL-cholesterol (mg dl−1)

62 ± 15

50 ± 11

<0.0001

ALT (IU l−1)

18 (9-27)

20 (9-32)

<0.0001

AST (IU l−1)

23 (16-30)

24 (16-32)

<0.0001

NAFLD, hepatic fat content ≥5.5% (n = 6,318)

2,416 (14.0)

3,902 (23.7)

<0.0001

PNPLA3, p.148M/M

7,571 (4.7)

8,814 (4.7)

0.93

  1. Upper panel: 1,861 individuals at risk of NAFLD in the cross-sectional Liver Biopsy Cohort. Lower panel: 125 dysmetabolic individuals used as transcriptomic cohort. The impact of the sex was estimated by unadjusted logistic regression models. AST, aspartate transaminase; N/A, not available.
  2. aNo woman was on estrogen therapy and three had polycystic ovary syndrome.
  3. bOne woman was on estroprogestinic therapy and one had polycystic ovary syndrome.
  4. cNo woman among cases was on hormonal therapy.
  5. dSeven women (5.7%) among cases at menopause or postmenopause were on hormonal therapy.