Volume 29, Issue 4, 2020
DOI: 10.24205/03276716.2020.802
Association between gallstone diseases and six gene SNPs linked to lipid traits in the Chinese Population
Abstract
Background: The association between six gene SNPs, namely PCSK9 p. Arg93Cys (rs151193009), LDLR p. Arg257Trp (rs200990725), CETP p. Asp459Gly (rs2303790), PKD1L3 p. Thr429Ser (rs7185272), PNPLA3 p. Ile148Met (rs738409), and TEAD2 p. Asp12Asn (rs142665148), and lipid metabolism has been reported in Journal of Nature Communications. Abnormal lipid metabolism is an important risk factor for gallstone disease. Gallstones are categorized into three sub-types: cholesterol, pigment, and mixed gallstones, based on composition. In this study, the association between these six gene SNPs and gallstone disease was investigated, and differences in the degree of mutations among the three subtypes of gallstone were determined.
Method: Venous blood (5 ml) and gallstones were collected from 100 patients who were treated as gallstone group. In addition, 5 ml of samples of venous blood were taken from 30 healthy volunteers who served as control group. Fourier transform infrared spectroscopy was used to determine gallstone components. There were two gallstone groups: cholesterol-type and non-cholesterol-type gallstone groups. Then, Mass ARRAY mass spectrometer was used to identify the mutants of the loci in the blood samples, and also for analysis of differences between the groups.
Results: 1. Significant difference was found between the gallstone and control groups in the degree of mutation in TEAD2 (rs142665148; p=0.039<0.05). The degree of mutation in TEAD2 (rs142665148) in the gallstone group was significantly higher than in the control group. No significant differences were found in the degree of mutations in PKD1L3 (rs7185272), PNPLA3 (rs738409), PCSK9 (rs151193009), LDLR (rs200990725), and CETP (rs2303790) between the gallstone and control groups (p>0.05). 2. Significant differences were found in the degrees of mutations in PKD1L3 (rs7185272) and PNPLA3 (rs738409) between the cholesterol-type and non-cholesterol-type gallstone groups (p <0.05). The degrees of mutation in PKD1L3 (rs7185272) and PNPLA3 (rs738409) in the cholesterol-type gallstone group were significantly higher than those in the non-cholesterol-type gallstone group. 3. No significant differences were found in degree of mutations in PCSK9 (rs151193009), LDLR (rs200990725), CETP (rs2303790), and TEAD2 (rs142665148) between the cholesterol-type and non-cholesterol-type gallstone groups (p >0.05).
Conclusion: 1. SNPs in TEAD2 (rs142665148), PKD1L3 (rs7185272), and PNPLA3 (rs738409) are associated with gallstone diseases. 2. Associations of SNPs in PKD1L3 (rs7185272) and PNPLA3 (rs738409) are more significant in the cholesterol-type gallstones than in the non-cholesterol-type type. There are significant differences in association of SNPs in TEAD2 (rs142665148) between the cholesterol-type and non-cholesterol-type gallstones.
Keywords
Lipid trait, gallstone disease, Fourier transform infrared spectrum, MassARRAY mass spectrometer, SNP