Genetic Variation of SAMM50 Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients
Abstract
:1. Introduction
2. Results
2.1. Study Population
2.2. Genotype Distribution
2.3. Frequency of the SAMM50 Minor Variants
2.4. Uni- and Multivariate Analysis for Various Risk Factors
2.5. Analysis of Linkage Disequilibrium between SAMM50 Variants and the PNPLA3 148M Variant
3. Patients and Methods
3.1. Patients
3.2. Methods
Determination of SAMM50 and PNPLA3 Genotypes
3.3. Statistical Analysis
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ANOVA | Analysis of Variance |
ALT | alanine aminotransferase |
AST | aspartate aminotransferase |
HCC | hepatocellular carcinoma |
HCV | hepatitis C virus |
HSD17B13 | 17β-Hydroxysteroid dehydrogenase type 13 |
GGT | Gamma-glutamyl transferase |
MAF | minor allele frequency |
MELD | Model for End-Stage Liver Disease |
NAFLD | non-alcoholic fatty liver disease |
NASH | non-alcoholic steatohepatitis |
NF-kB | nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells |
PNPLA3 | patatin-like phospholipase domain-containing protein 3 |
OR | odds ratio |
SAMM50 | Sorting and assembly machinery component 50 homolog |
TLR | toll-like receptor |
TM6SF2 | Transmembrane 6 superfamily 2 |
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Alcohol-Associated Cirrhosis | HCV HCC | Alcohol Misuse without Cirrhosis | Healthy Controls | ||
---|---|---|---|---|---|
with HCC | without HCC | ||||
Total number | 386 | 674 | 134 | 266 | 237 |
Age, mean (range) | 63.5 (36–87) a,b | 56.4 (27–92) c,d | 59.6 (38–82) d | 42.5 (18–81) e | 39.6 (20–75) |
Sex (% male/female) | 88.3/11.7 f | 70.6/29.4 g,h | 62.1/37.9 g | 85.4/14.6 i | 58.6/41.4 |
Bilirubin [mg/dL], (Mean ± SD) | 2.78 ± 4.16 j | 4.00 ± 6.71 g | 2.63 ± 3.49 | 0.80 ± 1.22 | n.d. |
ALT [IU/L], (Mean ± SD) | 49.2 ± 56.7 | 43.1 ± 110.0 | 71.9 ± 56.2 | 44.5 ± 49.9 | n.d. |
AST [IU/L], (Mean ± SD) | 88.8 ± 109.8 k | 72.5 ± 168.5 | 85.9 ± 81.1 | 53.4 ± 65.4 | n.d. |
GGT [IU/L], (Mean ± SD) | 273.5 ± 335.2 k,l | 197.1 ± 227.1 | 118.6 ± 127.0 | 203.4 ± 381.6 | n.d. |
Platelet count [* 103/µL], (Mean ± SD) | 150.9 ± 90.8 g | 152.3 ± 118.0 g | 111.4 ± 71.2 g | 229.3 ± 85.2 | n.d. |
MELD (Mean ± SD) | 13.7 ± 6.8 n | 16.8 ± 7.2 | 15.2 ± 5.0 | n.d. | n.d. |
Diabetes (%) | 46.4 m | 22.9 | 17.9 | n.d. | n.d. |
Genotype | Alcohol-Associated Cirrhosis (n = 1060) | HCV HCC (n = 134) | Alcohol Misuse without Cirrhosis (n = 266) | Healthy Controls (n = 237) | |
---|---|---|---|---|---|
with HCC n = 386 | without HCC n = 674 | ||||
SAMM50 rs3827385 | |||||
TT | 162 (42.0%) | 381 (56.5%) | 84 (62.7%) | 176 (66.2%) | 160 (67.5%) |
TC | 178 (46.1%) a,d,g | 246 (36.5%) b | 40 (29.9%) | 84 (31.6%) | 65 (27.4%) |
CC | 46 (11.9%) a,d,f | 47 (7.0%) e | 10 (7.5%) | 6 (2.3%) | 12 (5.1%) |
allele frequency T/C | 65.0%/35.0% a,d,g | 74.8%/25.2% b | 81.2%/18.8% | 82.0%/18.0% | 81.2%/18.8% |
SAMM50 rs3761472 | |||||
AA | 158 (40.9%) | 374 (55.5%) | 87 (64.9%) | 180 (67.7%) | 157 (66.2%) |
AG | 179 (46.4%) a,d,g | 248 (36.8%) c,f | 38 (28.4%) | 77 (28.9%) | 67 (28.3%) |
GG | 49 (12.7%) a,d,g | 52 (7.7%) | 9 (6.7%) | 9 (3.4%) | 13 (5.5%) |
allele frequency A/G | 64.1%/35.9% a,d,g | 73.9%/26.1% c | 79.1%/20.9% | 82.1%/17.9% | 80.4%/19.6% |
PNPLA3 rs738409 | |||||
CC | 96 (24.9%) | 280 (41.5%) | 64 (47.8%) | 146 (54.9%) | 129 (54.4%) |
GC | 199 (51.6%) a,d,g | 306 (45.4%) c | 54 (40.3%) | 104 (39.1%) | 89 (37.6%) |
GG | 91 (23.6%) a,d,g | 88 (13.1%) c | 16 (11.9%) | 16 (6.0%) | 19 (8.0%) |
allele frequency C/G | 50.6%/49.4% a,d,g | 64.2%/35.8% d | 67.9%/32.1% | 74.4%/25.6% | 73.2%/26.8% |
Univariate Analysis | ||||
---|---|---|---|---|
95% CI | ||||
Parameter | P | OR | Lower | Upper |
Age | 4.0 × 10−24 | 1.086 | 1.069 | 1.103 |
Sex (male) | 1.1 × 10−9 | 3.151 | 2.178 | 4.559 |
Diabetes | 2.4 × 10−13 | 2.909 | 2.186 | 3.871 |
PNPLA3 148 (IM/MM) | 6.4 × 10−8 | 2.147 | 1.627 | 2.832 |
rs3827385 (TC/CC) | 6.0 × 10−6 | 1.798 | 1.396 | 2.316 |
rs3761472 (AG/GG) | 6.0 × 10−6 | 1.799 | 1.396 | 2.318 |
Multivariate Analysis * | ||||
95% CI | ||||
Parameter | P | OR | Lower | Upper |
Age | 1.2 × 10−16 | 1.078 | 1.059 | 1.097 |
Sex (male) | 8.1 × 10−8 | 3.174 | 2.081 | 4.840 |
Diabetes | 6.3 × 10−5 | 1.930 | 1.399 | 2.662 |
PNPLA3 148M | 1.6 × 10−5 | 2.083 | 1.492 | 2.909 |
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Nischalke, H.D.; Schmalz, F.; Buch, S.; Fischer, J.; Möller, C.; Matz-Soja, M.; Krämer, B.; Langhans, B.; Klüners, A.; Soyka, M.; et al. Genetic Variation of SAMM50 Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients. Int. J. Mol. Sci. 2022, 23, 15353. https://doi.org/10.3390/ijms232315353
Nischalke HD, Schmalz F, Buch S, Fischer J, Möller C, Matz-Soja M, Krämer B, Langhans B, Klüners A, Soyka M, et al. Genetic Variation of SAMM50 Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients. International Journal of Molecular Sciences. 2022; 23(23):15353. https://doi.org/10.3390/ijms232315353
Chicago/Turabian StyleNischalke, Hans Dieter, Franziska Schmalz, Stephan Buch, Janett Fischer, Christine Möller, Madlen Matz-Soja, Benjamin Krämer, Bettina Langhans, Alexandra Klüners, Michael Soyka, and et al. 2022. "Genetic Variation of SAMM50 Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients" International Journal of Molecular Sciences 23, no. 23: 15353. https://doi.org/10.3390/ijms232315353