TABLE 1.
Clinical Relevance of TM6SF2
| Reference | Sample Size | Ethnicity/Place of Study | Plasma Lipids | Liver Enzymes | HTGC/Method | NASH | Fibrosis | Cirrhosis | HCC | CVS |
|---|---|---|---|---|---|---|---|---|---|---|
| Kozlitina et al.( 11 ) | DHS (n = 2,736) | non‐Hispanic African Americans, non‐Hispanic, European Americans, Hispanics and other ancestry | LDL‐C↓ and TG↓ | ALT↑ | ↑/1H‐MRS | NM | NM | NM | NM | NM |
| Dallas BioBank (n = 8,585) | European‐Americans | LDL‐C↓ and TG↓ | ALT↑ | ↑/1H‐MRS | NM | NM | NM | NM | NM | |
| Copenhagen City Heart Study and Copenhagen General Population Study (n = 73,532) | Denmark | LDL‐C↓ and TG↓ | ALT↑ and AST↑ | ↑/1H‐MRS | NM | NM | NM | NM | NM | |
| Holmen et al.( 12 ) | N = 92,605 | Europeans | TC↓ and TG↓ | NM | NM | NM | NM | NM | NM | MI↓ |
| Liu et al.( 46 ) | Discovery cohort (n = 349) | European Caucasian | NM | NM | ↑/biopsy | ↑ | ↑ | Not clear | NM | NM |
| Validation cohort (n = 725) | European Caucasian | NM | NM | ↑/biopsy | NA | ↑ | Not clear | NM | NM | |
| NAFLD‐HCC cohort (n = 99) | European Caucasian | NM | NM | NM | NM | NM | NM | ↑ | NM | |
| Wong et al.( 47 ) | HK‐MRS (n = 922) | Chinese | TC↓, LDL‐C↓ and TG↓ | NM | ↑/1H‐MRS | NM | NA | NA | NM | NM |
| Sookoian et al.( 14 ) | N = 361 | Argentina | TC↓, LDL‐C: NA, and TG: NA | NA | ↑/biopsy | NM | NA | NM | NM | CVD risk↓ |
| Dongiovanni et al.( 16 ) | Liver biopsy cohort (n = 1,201) | Italy, Finland | TC↓, LDL‐C: NA and TG↓ | NA | ↑/biopsy | ↑ | ↑ | NM | NM | NM |
| carotid atherosclerosis cohort (427) | Italy | NM | NM | NM | NM | NM | NM | NM | Carotid plaques↓ | |
| SOS cohort (n = 1,819) | Swedish | ALT↑ and AST↑ | NM | NM | NM | NM | NM | NM | CVD events↓ | |
| Zhou et al.( 45 ) | N = 300 | Finnish | LDL‐C and TG: NA | ALT and AST: NA | ↑/1H‐MRS | NM | NM | NM | NM | NM |
| Akuta et al.( 48 ) | Patients with biopsy‐proven NAFLD (n = 211) | Japanese | NM | NM | NM | NA | NA | NM | NM | NM |
| Goffredo et al.( 41 ) | Children/adolescents with obesity (n = 402) | Caucasians | TC↓, and LDL‐C↓ | ↑ trend | ↑/MRI | NM | NM | NM | NM | NM |
| Children/adolescents with obesity (n = 266) | African Americans | NA | NA | ↑/MRI | NM | NM | NM | NM | NM | |
| Children/adolescents with obesity (n = 289) | Hispanics | TC↓, and LDL‐C↓ | ALT↑ and AST↑ | ↑/MRI | NM | NM | NM | NM | NM | |
| Grandone et al.( 57 ) | Children/adolescents with obesity (n = 1,010) | Italy | TC↓, LDL‐C↓ and TG↓ | ALT↑ and AST: NA | ↑/ultrasound | NM | NM | NM | NM | NM |
| Mancina et al.( 56 ) | Children/adolescents with obesity (n = 423) | Italy | NM | NA | ↑/ultrasound | NM | NM | NM | NM | NM |
| O'Hare et al. ( 60 ) | GHS bariatric surgery cohort (n = 983) | NA | NM | ↑/biopsy | ↑ | ↑ | NA | NM | NM | |
| ACDRP cohorts (n = 3,556) | Caucasian | TC↓, LDL‐C↓ and TG↓ | NA | NM | NM | NM | NM | NM | NM | |
| Krawczyk et al.( 49 ) | NAFLD Clinical Study Group project (n = 515) | German | NM | ALT↑ and AST↑ | ↑/MRI | NM | NA | NM | NM | NM |
| Liu et al.( 15 ) | N > 300,000 | European, African, South Asian, Hispanic or other ancestry | TC↓ and TG↓ | NM | ↑/CT | NM | NM | NM | NM | CAD↓ |
| Basyte‐Bacevice et al.( 50 ) | N = 1,012 | Lithuania | NM | NM | NM | NM | NA | NA | NM | NM |
| Anstee et al.( 42 ) | Histologically characterized cohort (1,483 biopsied NAFLD cases and 17,781 controls) | Europeans | NM | NM | ↑/biopsy | ↑ | NM | NM | NM | NM |
| Parisinos et al.( 43 ) | UK BioBank Cohort (n = 14,440) | Europeans | LDL‐C↓ and TG↓ | ALT↑ and AST↑ | ↑/MRI | NM | NM | ↑ | NM | CAD↓ |
| Chen et al.( 44 ) | UK BioBank (1,088 cases vs. 407,873 controls) and Michigan Genomics Initiative (875 cases of cirrhosis vs. 30,346 controls) | UK, US | LDL‐C↓ and TG↓ | ALT↑ | NM | NM | NM | ↑ | NM | NM |
Abbreviations: ↑, increase or positive association; ↓, decrease or negative association; ACDRP, Amish Complex Disease Research Program; AST, aspartate transaminase; CAD, coronary artery disease; CT, computed tomography; GHS, Geisinger Health System; HK‐MRS, Hong Kong, magnetic resonance spectroscopy; 1H‐MRS, proton nuclear magnetic resonance spectroscopy; HTGC, hepatic triglyceride content; MI, myocardial infarction; MRI, magnetic resonance imaging; NA, no association; NM, not mentioned; SOS, Obese Subjects Study; UK, United Kingdom; US, United States.