PNPLA3 rs738409 underlies treatment response in nonalcoholic fatty liver disease

Table 1 Effect of Patatin-like phospholipase domain-containing protein 3 rs738409 C > G p.I148M on therapeutic response in nonalcoholic fatty liver disease

Study	Country	Duration	Number	Intervention	Results
Sevastianova et al[20] (2011)	Finland, Italy	6 d	18 (all in intervention group)	Hypocaloric (1000-kcal deficit/d), low-carbohydrate diet (< 30 g/d)	Δliver fata
Shen et al[19] (2015)	China	12 mo	Intervention group (n = 77), control group (n = 77)	Exercise and limitation on caloric intake	ΔIHTGd, ΔBody weightc, ΔWCc, ΔWHRc, ΔTCc, ΔHDL-Cd
Milkiewicz et al[22] (2016)	Poland	4 mo	323 (143 in intervention group; 180 in control group)	Diet with 500 kcal resriction for subjects (BMI > 25); maintance of body weight for subjects (BMI ≤ 25)	ΔWHRc
Scorletti et al[28] (2015)	United States	15-18 mo	Omacor®: n = 51; placebo: n = 52	Omacor®, 4 g/d (460 mg EPA + 380 mg DHA for 1 g Omacor)	Δliver fate
Nobili et al[29] (2013)	Italy	24 mo	DHA 250 mg/d (n = 20), DHA 500 mg/d (n = 20), placebo group (n = 20)	DHA 250 mg/d, DHA 500 mg/d, or placebo	Severe steatosisgh, TGi ALTi
Dongiovanni et al[35] (2015)	Italy, Finland	6 mo	107 (all in intervention group)	Drug: simvastatin (49%), rosuvastatin (27%), atorvastatin (17%), pravastatin (4%), fluvastatin (2%) Intensity: high (15%), moderate (73%), low (12%)	Risk of NASHk
Kan et al[40] (2016)	Japan	33.1 mo	41 (all in alogliptin group)	Alogloptin, 25 mg/d	ΔALT, ΔAST, ΔHbA1cm
Krawczyk et al[57] (2016)	Spain	12 mo	84 (all in surgery group)	Gastic bypass surgery; gastric sleeve surgery	Δweightp, Δliver fato
Palmer et al[59] (2012)	Sweden	2 yr; 10 yr	3473 (2nd year: 1624 in surgery group; 10th year: 1355 in surgery group)	nonadjustable or adjustable banding; vertical banded gastroplasty; gastric bypass	ΔHOMA-IRq, Δserum TGq, ΔALTs

^aP < 0.05, PNPLA3 148M/M vs PNPLA3 148I/I;

^cP < 0.05,

^dP < 0.01, among PNPLA3 148I/I, 148I/M, and 148M/M in intervention group;

^eP < 0.05 PNPLA3 148I/I +148I/M vs PNPLA3 148M/M;

^hP < 0.001, PNPLA3 148M/M vs PNPLA3 148 I/M and

^gP < 0.05, PNPLA3 148I/M vs PNPLA3 148 I/I;

ⁱP < 0.05, PNPLA3 148M/M vs 148I/M;

^kP < 0.001, PNPLA3 148I/I vs 148I/M or PNPLA3 148I/I vs 148M/M;

^mΔHbA1c correlates to ΔALT (P = 0.001) and ΔAST (P = 0.014) in patients with PNPLA3 rs738409 C/G+G/G;

^oP < 0.05,

^pP < 0.01, PNPLA3 148I/I vs PNPLA3 148I/M+148M/M;

^qP < 0.05, among PNPLA3 148I/I, 148I/M, and 148M/M in surgery group (2^nd, 10^th year);

^sP < 0.001, among PNPLA3 148I/I, 148I/M, and 148M/M in surgery group (2^nd year). ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BMI: Body mass index; IHTG: Intrahepatic triglyceride content; HbA1c: Hemoglobin A1c; HDL-C: High-density lipoprotein-cholesterol; HOMA-IR: Homeostasis model assessment-insulin resistance; TC: Total cholesterol; TG: Triglycerides; WC: Waist circumference; WHR: Waist-to-hip ratio.