NAFLD-related SNPs are linked to changes in liver fat, measured by CAP score, and serum lipids in response to a 3-week sugar sweetened beverage intervention: A pilot study

Abstract

Studies show that increased consumption of sugar sweetened beverage (SSB) is linked to non-alcoholic fatty liver disease (NAFLD), a condition characterized by excess fat accumulation in hepatocytes. Genetic factors also influence NAFLD. We conducted a clinical trial (NCT03783195) to determine if SNPs related to liver fat are associated with its changes in response to a 3-week SSB intervention in Caucasian adolescents and young adults. Fifteen participants (Males-5, Females-10, mean age 25.5 ± 9 yrs) consumed a beverage, daily for 3 weeks, consisting of fructose:glucose in 60:40 ratio. Liver fat was measured by transient elastography through controlled attenuation parameter (CAP) score. At baseline, the CAP score was 212.5±10.1dB/m and was not significantly different between sexes. We genotyped ten liver-fat related SNPs, of which rs1227756 in COL13A1 (β=-22.4±7.5, p<0.05) was associated with baseline CAP score. Individuals carrying AA alleles had significantly higher CAP score than those carrying GG (234±34.7dB/m vs. 188 ± 25.3 dB/m). The CAP score decreased post SSB intervention, and the change was significantly associated with rs2228603 in NCAN (β=-20.1± 7.6, p<0.05). The T allele carriers showed a greater reduction in CAP score as compared to CC carriers (Mean ± SE -23.3 ± 5.8 dB/m vs. -18.24 ± 43.2 dB/m). Significant associations were also observed between serum HDL and rs1260326 in GCKR and triglycerides and rs58542926 in TMS6F2. This pilot study shows a potential role for genetics in liver fat changes in response to SSB intervention that warrants a detailed investigation in a larger sample for a longer duration.