AIM To test the hypothesis that K8/K18 variants predispose humans to non-alcoholic fatty liver disease(NAFLD) progression and its metabolic phenotypes. METHODS We selected a total of 373 unrelated adult subjects from ...AIM To test the hypothesis that K8/K18 variants predispose humans to non-alcoholic fatty liver disease(NAFLD) progression and its metabolic phenotypes. METHODS We selected a total of 373 unrelated adult subjects from our Physical Examination Department, including 200 unrelated NAFLD patients and 173 controls of both genders and different ages. Diagnoses of NAFLD were established according to ultrasonic signs of fatty liver. All subjects were tested for population characteristics, lipid profile, liver tests, as well as glucose tests. Genomic DNA was obtained from peripheral blood with a DNeasy Tissue Kit. K8/K18 coding regions were analyzed, including 15 exons and exon-intron boundaries. RESULTS Among 200 NAFLD patients, 10(5%) heterozygouscarriers of keratin variants were identified. There were 5 amino-acid-altering heterozygous variants and 6 non-coding heterozygous variants. One novel aminoacid-altering heterozygous variant(K18 N193S) and three novel non-coding variants were observed(K8 IVS5-9A→G, K8 IVS6+19G→A, K18 T195T). A total of 9 patients had a single variant and 1 patient had compound variants(K18 N193S+K8 IVS3-15C→G). Only one R341 H variant was found in the control group(1 of 173, 0.58%). The frequency of keratin variants in NAFLD patients was significantly higher than that in the control group(5% vs 0.58%, P = 0.015). Notably, the keratin variants were significantly associated with insulin resistance(IR) in NAFLD patients(8.86% in NAFLD patients with IR vs 2.5% in NAFLD patients without IR, P = 0.043).CONCLUSION K8/K18 variants are overrepresented in Chinese NAFLD patients and might accelerate liver fat storage through IR.展开更多
基金Supported by National Natural Science Foundation of China,No.81670518 and No.81170392The Science and Technology Project of Guangdong Province,China,No.2013B021800290 and No.2014A020212118Guangzhou Science and Technology Innovation Commission,China,No.201604020155
文摘AIM To test the hypothesis that K8/K18 variants predispose humans to non-alcoholic fatty liver disease(NAFLD) progression and its metabolic phenotypes. METHODS We selected a total of 373 unrelated adult subjects from our Physical Examination Department, including 200 unrelated NAFLD patients and 173 controls of both genders and different ages. Diagnoses of NAFLD were established according to ultrasonic signs of fatty liver. All subjects were tested for population characteristics, lipid profile, liver tests, as well as glucose tests. Genomic DNA was obtained from peripheral blood with a DNeasy Tissue Kit. K8/K18 coding regions were analyzed, including 15 exons and exon-intron boundaries. RESULTS Among 200 NAFLD patients, 10(5%) heterozygouscarriers of keratin variants were identified. There were 5 amino-acid-altering heterozygous variants and 6 non-coding heterozygous variants. One novel aminoacid-altering heterozygous variant(K18 N193S) and three novel non-coding variants were observed(K8 IVS5-9A→G, K8 IVS6+19G→A, K18 T195T). A total of 9 patients had a single variant and 1 patient had compound variants(K18 N193S+K8 IVS3-15C→G). Only one R341 H variant was found in the control group(1 of 173, 0.58%). The frequency of keratin variants in NAFLD patients was significantly higher than that in the control group(5% vs 0.58%, P = 0.015). Notably, the keratin variants were significantly associated with insulin resistance(IR) in NAFLD patients(8.86% in NAFLD patients with IR vs 2.5% in NAFLD patients without IR, P = 0.043).CONCLUSION K8/K18 variants are overrepresented in Chinese NAFLD patients and might accelerate liver fat storage through IR.
