Zhang RN, Shen F, Pan Q, Cao HX, Chen GY, Fan JG. PPARGC1A rs8192678 G>A polymorphism affects the severity of hepatic histological features and nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease . World J Gastroenterol 2021; 27(25): 3863-3876 [PMID: 34321850 DOI: 10.3748/wjg.v27.i25.3863]
Corresponding Author of This Article
Jian-Gao Fan, MD, PhD, Director, Professor, Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, No. 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China. fanjiangao@xinhuamed.com.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Jul 7, 2021; 27(25): 3863-3876 Published online Jul 7, 2021. doi: 10.3748/wjg.v27.i25.3863
Table 1 Clinical characteristics of patients with nonalcoholic fatty liver disease and controls
Variables
NAFLD (n = 59)
Controls (n = 93)
P value
Sex (M/F)
43/16
59/34
0.227
Age (year)
38.20 ± 13.78
42.20 ± 11.05
0.039
BMI (kg/m2)
27.31 ± 3.31
23.06 ± 2.74
< 0.0001
ALT (U/L)
70.56 ± 47.6
24.98 ± 16.07
< 0.0001
GGT (U/L)
72.75 ± 55.22
25.94 ± 18.17
< 0.0001
ALP (U/L)
97.07 ± 44.73
96.50 ± 32.54
0.347
TC (mmol/L)
4.86 ± 0.86
4.39 ± 0.89
0.001
TG (mmol/L)
1.99 ± 1.25
1.14 ± 0.74
< 0.0001
HDL-C (mmol/L)
1.20 ± 0.28
1.23 ± 0.28
0.177
LDL-C (mmol/L)
2.83 ± 0.7
2.24 ± 0.50
< 0.0001
FBG (mmol/L)
5.93 ± 2.62
5.31 ± 0.79
0.941
UA (μmol/L)
361.32 ± 105.78
274.25 ± 76.53
< 0.0001
CAP (dB/m)
313 (277-351)
212 (172-232)
< 0.0001
LSM (kPa)
7.7 (5.6-12)
5.25 (4.1-7.0)
< 0.0001
Hypertension, n (%)
22 (37.29%)
15 (16.13%)
0.003
T2DM, n (%)
7 (11.86%)
1 (1.08%)
0.005
Obesity, n (%)
41 (69.49%)
19 (20.43%)
< 0.0001
Steatosis (S, n)
S1/S2/S3
25/25/9
/
/
Activity (A, n)
A0/A1/A2/A3/A4
1/12/16/22/8
/
/
Fibrosis (F, n)
F0/F1/F2/F3/F4
11/29/8/7/4
/
/
Table 2 Clinical characteristics of patients with nonalcoholic steatohepatitis and nonalcoholic fatty liver among patients with nonalcoholic fatty liver disease
Variable
NAFL (n = 22)
NASH (n = 37)
P value
Sex (M/F)
17/5
26/11
0.559
Age (year)
37.23 ± 13.64
38.78 ± 14.01
0.605
BMI (kg/m2)
27.07 ± 3.69
27.38 ± 3.17
0.675
ALP (U/L)
102.96 ± 52.34
93.56 ± 39.91
0.982
GGT (U/L)
38.00 (23.80-69.03)
69.70 (39.00-85.50)
0.023
ALT (U/L)
46.00 (30.33-64.95)
71.40 (46.9-111.70)
0.006
TC (mmol/L)
5.03 ± 1.04
4.76 ± 0.72
0.801
TG (mmol/L)
1.91 ± 0.74
2.04 ± 1.48
0.532
HDL-C (mmol/L)
1.21 ± 0.28
1.19 ± 0.28
0.903
LDL-C (mmol/L)
2.97 ± 0.91
2.72 ± 0.49
0.444
FBG (mmol/L)
6.43 ± 3.59
5.62 ± 1.77
0.318
UA (μmol/L)
360.91 ± 107.80
361.62 ± 106.22
0.482
CAP (dB/m)
295.50 (249.25-345.00)
333.00 (296.25-356.25)
0.038
LSM (kPa)
6.20 (4.55-9.95)
9.60 (6.50-12.85)
0.008
Obesity, n (%)
16 (72.73)
25 (60.97)
0.677
Hypertension, n (%)
8 (36.36)
14 (37.84)
0.910
T2DM, n (%)
3 (13.64)
4 (10.81)
0.746
Table 3 Genotype distribution of PPARGC1A rs8192678 and patatin-like phospholipase domain-containing protein 3 rs738409 in patients with nonalcoholic fatty liver disease and controls
Genotype
NAFLD (n = 59)
Controls (n = 93)
χ2
P value
OR (95%CI)
PPARGC1A rs8192678
GG
14 (23.73%)
39 (41.94%)
GA
37 (62.71%)
37 (39.78%)
7.148
0.008
2.786 (1.300-5.962)
AA
8 (13.56%)
17 (18.28%)
0.262
0.609
1.311 (0.464-3.704)
GA+AA
45 (76.27%)
54 (58.06%)
5.269
0.022
2.321 (1.121-4.806)
PNPLA3 rs738409
CC
12 (20.34%)
35 (37.63%)
CG
27 (45.76%)
43 (46.24%)
2.152
0.142
1.831 (0.812-4.131)
GG
20 (33.90%)
15 (16.13%)
8.423
0.004
3.889 (1.524-9.926)
CG + GG
47 (79.56%)
58 (62.37%)
5.055
0.025
2.364 (1.105-5.055)
Table 4 Association tests of PPARGC1A rs8192678 polymorphism between different groups
PPARGC1A rs8192678
Case
Control
Dominant model
GG
GA
AA
GG
GA
AA
χ2
P value
OR (95%CI)
NAFLD vs Control
14
37
8
39
37
17
5.269
0.022
2.321 (1.121-4.806)
NASH vs Control
5
28
4
39
37
17
9.550
0.002
4.622 (1.653-12.929)
NASH vs NAFL
5
28
4
9
9
4
5.721
0.017
4.431 (1.245-15.763)
Obese vs nonobese participants
17
33
10
36
41
15
1.864
0.172
1.626 (0.807-3.276)
Obese NAFLD vs nonobese NAFLD
9
27
5
5
10
3
0.235
0.628
1.368 (0.384-4.865)
Obese NASH vs nonobese NASH
4
19
2
1
9
2
0.408
0.348
0.477 (0.047-4.806)
Obese NAFL vs nonobese NAFL
5
8
3
4
1
1
2.264
0.132
4.400 (0.596-32.501)
Obese NASH vs obese NAFL
4
19
2
5
8
3
1.324
0.250
2.386 (0.531-10.734)
Nonobese NASH vs nonobese NAFL
1
9
2
4
1
1
6.785
0.021
22.000 (1.540-314.292)
Table 5 Multiple logistic regression analysis of predictive factors for nonalcoholic fatty liver disease
Variables
B
S.E.
Wald
OR (95%CI)
P value
Age (year)
-0.031
0.015
4.236
0.970 (0.942-0.999)
0.040
Sex (Male)
-0.233
0.385
0.365
0.793 (0.373-1.686)
0.546
PPARGC1A rs8192678 A allele
0.789
0.388
4.148
2.202 (1.030-4.705)
0.042
PNPLA3 rs738409 G allele
0.857
0.403
4.524
2.356 (1.070-5.191)
0.033
Table 6 Association of the PPARGC1A genotypes with steatosis, activity, and fibrosis in patients with nonalcoholic fatty liver disease
Table 7 Biochemical and genetic characteristics of patients with nonobese nonalcoholic fatty liver disease
Variables
NAFL (n = 6)
NASH (n = 12)
P value
Sex (M/F)
4/2
10/2
0.569
Age (year)
35.33 ± 18.44
39.67 ± 4.80
0.452
BMI (kg/m2)
22.83 ± 1.61
23.69 ± 0.90
0.122
ALP (U/L)
123.32 ± 77.62
84.25 ± 23.28
0.426
GGT (U/L)
28.50 (21.18-85.00)
73.25 (54.75-99.25)
0.068
ALT (U/L)
42.00 (21.78-78.50)
71.15 (41.10-115.25)
0.325
TC (mmol/L)
5.11 ± 0.55
4.96 ± 1.02
0.606
TG (mmol/L)
2.00 ± 0.43
1.77 ± 0.95
0.371
HDL-C (mmol/L)
1.10 ± 0.16
1.24 ± 0.44
0.943
LDL-C (mmol/L)
3.16 ± 0.46
2.82 ± 0.80
0.524
FBG (mmol/L)
5.03 ± 0.94
5.24 ± 0.85
0.587
UA (μmol/L)
360.86 ± 167.34
354.17 ± 67.43
0.684
CAP (dB/m)
257.00 ± 57.03
316.73 ± 43.48
0.056
LSM (kPa)
6.95 ± 4.07
6.79 ± 2.06
0.421
PPARGC1A rs8162678
GG, n (%)
4 (66.67)
1 (8.33)
GA + AA, n (%)
2 (33.33)
11 (91.67)
0.021
PNPLA3 rs738409
CC, n (%)
2 (33.33)
1 (8.33)
CG + GG, n (%)
4 (66.67)
11 (91.67)
0.245
Citation: Zhang RN, Shen F, Pan Q, Cao HX, Chen GY, Fan JG. PPARGC1A rs8192678 G>A polymorphism affects the severity of hepatic histological features and nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease . World J Gastroenterol 2021; 27(25): 3863-3876