Collagen Formation Assessed by N‐Terminal Propeptide of Type 3 Procollagen Is a Heritable Trait and Is Associated With Liver Fibrosis Assessed by Magnetic Resonance Elastography. Issue 1 (29th April 2019)

• Record Type: Journal Article
• Authors: Caussy, Cyrielle; Bhargava, Meera; Villesen, Ida F.; Gudmann, Natasja S.; Leeming, Diana J.; Karsdal, Morten A.; Faulkner, Claire; Bao, Denny; Liu, Amy; Lo, Min‐Tzu; Bettencourt, Ricki; Bassirian, Shirin; Richards, Lisa; Brenner, David A.; Chen, Chi‐Hua; Sirlin, Claude B.; Loomba, Rohit
• Is Part Of: Hepatology. Volume 70:Issue 1(2019)
• Page Start: 127
• Page End: 141
• Publication Date: 2019-04-29
• Subjects: Heart -- Diseases -- Nursing -- Periodicals; Lungs -- Diseases -- Nursing -- Periodicals; Intensive care nursing -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1002/hep.30610
• Languages: English
• ISSNs: 0270-9139

Abstract

Abstract : N‐terminal propeptide of type 3 procollagen (PRO‐C3) is a biomarker of liver fibrosis in nonalcoholic fatty liver disease (NAFLD). This study examines the association between PRO‐C3 concentration and liver fibrosis assessed by magnetic resonance elastography (MRE)–measured stiffness (MRE‐stiffness) and the heritability of PRO‐C3 concentration in a cohort of twins and families with and without NAFLD. We performed a cross‐sectional analysis of a well‐characterized prospective cohort of 306 participants, including 44 probands with NAFLD‐cirrhosis and their 72 first‐degree relatives, 24 probands with NAFLD without advanced fibrosis and their 24 first‐degree relatives, and 72 controls without NAFLD and their 72 first‐degree relatives. Liver steatosis was assessed by magnetic resonance imaging proton density fat fraction, and liver fibrosis was assessed by MRE‐stiffness. Serum PRO‐C3 was assessed by competitive, enzyme‐linked immunosorbent assay. We assessed the familial correlation of PRO‐C3 concentration, the shared gene effects between PRO‐C3 concentration and liver steatosis and fibrosis, and the association between PRO‐C3 concentration and genetic variants in the patatin‐like phospholipase domain–containing 3 ( PNPLA3 ), transmembrane 6 superfamily member 2 ( TM6SF2 ), membrane‐bound O‐acyltransferase domain–containing ( MBOAT ), and glucokinase regulator ( CGKR ) genes. In multivariable‐adjusted models including age, sex, body mass index, and ethnicity, serum PRO‐C3 correlated strongly with liver fibrosis ( r 2 = 0.50, P < 0.001) and demonstrated robust heritability ( h 2, 0.36; 95% confidence interval [CI], 0.07, 0.59; P = 0.016). PRO‐C3 concentration and steatosis had a strong genetic correlation (shared genetic determination: 0.62; 95% CI, 0.236, 1.001; P = 0.002), whereas PRO‐C3 concentration and fibrosis had a strong environmental correlation (shared environmental determination: 0.55; 95% CI, 0.317, 0.717; P < 0.001). PRO‐C3 concentrations were higher in carriers of the TM6SF2 rs58542926‐T allele compared with noncarriers: 15.7 (± 10.5) versus 10.8 (± 5.7) ng/L ( P = 0.047). Conclusion : Serum PRO‐C3 correlates with MRE‐assessed fibrosis, is heritable, shares genetic correlation with liver steatosis and shares environmental correlation with liver fibrosis. PRO‐C3 concentration appears to be linked to both fibrosis and steatosis and increased in carriers of the TM6SF2 rs58542926 risk allele.