Association of Nonalcoholic Fatty Liver Disease and Coronary Artery Disease with FADS2 rs3834458 Gene Polymorphism in the Chinese Han Population.
ABSTRACT: Background:Nonalcoholic fatty liver disease (NAFLD) patients are often prone to coronary artery disease (CAD), and CAD is found to be the main cause of death in NAFLD patients. The purpose of this study was to investigate the association between fatty acid desaturase 2 (FADS2) rs3834458 polymorphism and serum FADS2 level with NAFLD and CAD in Chinese Han population. Materials and Methods:The serum level of FADS2 was detected by enzyme-linked immunosorbent assay (ELISA) in healthy people, NAFLD patients, and NAFLD patients combined with CAD (NAFLD+CAD). Polymerase chain reaction (PCR) was used to detect the genotypes of FADS2 rs3834458 in the three groups. Results:Body mass index (BMI), glucose (GLU), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) of the NAFLD group and the NAFLD+CAD group were higher than those of the healthy control group (P < 0.05); the HDL-C of the NAFLD+CAD group was significantly lower than that of the healthy people and the NAFLD group (P < 0.05). The serum FADS2 concentration in the NAFLD+CAD group was significantly higher than that in the NAFLD group (P < 0.05) and the healthy people (P < 0.05). There was no significant difference in genotype distribution (? 2 = 5.347, P < 0.497) and allele frequency (? 2 = 3.322, P = 0.345) between the three groups. Logistic regression analysis showed that the T allele was not an independent risk factor for CAD with NAFLD (OR = 1.62, 95% CI: 0.422-6.180). Conclusions:Serum FADS2 concentration was positively correlated with the susceptibility of NAFLD with CAD, while the polymorphism of rs3834458 was not associated with NAFLD with CAD.
Project description:Long-chain n-6 and n-3 PUFA (LC-PUFA), arachidonic acid (AA) (20:4n-6) and DHA (22:6n-3), are critical for optimal brain development. These fatty acids can be consumed directly from the diet, or synthesized endogenously from precursor PUFA by ?-5 (encoded by FADS1) and ?-6 desaturases (encoded by FADS2). The aim of this study was to determine the potential importance of maternal genetic variability in FADS1 and FADS2 genes to maternal LC-PUFA status and infant neurodevelopment in populations with high fish intakes. The Nutrition Cohorts 1 (NC1) and 2 (NC2) are longitudinal observational mother-child cohorts in the Republic of Seychelles. Maternal serum LC-PUFA was measured at 28 weeks gestation and genotyping for rs174537 (FADS1), rs174561 (FADS1), rs3834458 (FADS1-FADS2) and rs174575 (FADS2) was performed in both cohorts. The children completed the Bayley Scales of Infant Development II (BSID-II) at 30 months in NC1 and at 20 months in NC2. Complete data were available for 221 and 1310 mothers from NC1 and NC2 respectively. With increasing number of rs3834458 minor alleles, maternal concentrations of AA were significantly decreased (NC1 p=0.004; NC2 p<0.001) and precursor:product ratios for linoleic acid (LA) (18:2n-6)-to-AA (NC1 p<0.001; NC2 p<0.001) and ?-linolenic acid (ALA) (18:3n-3)-to-DHA were increased (NC2 p=0.028). There were no significant associations between maternal FADS genotype and BSID-II scores in either cohort. A trend for improved PDI was found among infants born to mothers with the minor rs3834458 allele.In these high fish-eating cohorts, genetic variability in FADS genes was associated with maternal AA status measured in serum and a subtle association of the FADS genotype was found with neurodevelopment.
Project description:Dietary essential polyunsaturated fatty acids (PUFAs) require fatty acid desaturases (FADS) for conversion to long-chain PUFAs (LCPUFAs), which are critical for many aspects of human health. A ?6-desaturase deficiency in a single patient was attributed to an insertion mutation in the FADS2 promoter. Later population studies have shown this thymidine nucleotide (T) insertion to be a common polymorphism (rs3834458). We examined correlations between rs3834458 variants and fatty acid evidence of FADS2 activity in a cohort of rheumatoid arthritis patients selected for low or nil consumption of n-3 LCPUFA as fish or fish oil. The presence of the T allele was associated with higher FADS2 activity, as indicated by higher conversion of plasma n-3 PUFA to LCPUFA. However, the T-insertion/deletion polymorphism did not affect FADS2 promoter activity in luciferase reporter assays in HepG2 or NIH/3T3 cells. Our results indicate that the polymorphism rs3834458 does not appear to directly affect FADS2 promoter activity and is not responsible for a previously reported ?6-desaturase deficiency.
Project description:BACKGROUND:Cardiovascular events are an independent risk factor for nonalcoholic fatty liver disease (NAFLD), which is the leading cause of mortality in NAFLD patients. Several recent studies demonstrated that adiponectin (Ad) polymorphisms were involved in the progression of NAFLD and coronary artery disease (CAD). However, reports on the association between Ad polymorphisms and the risk of developing CAD in NAFLD patients are lacking in a Northern Han Chinese population. OBJECTIVES:The present study was designed to evaluate the association between Ad gene polymorphisms (rs266729 and rs2241766) and the risk of developing CAD in Northern Han Chinese patients with NAFLD. MATERIALS AND METHODS:In this case-control study, using the polymerase chain reaction (PCR), Adrs266729 and rs2241766 gene polymorphisms were genotyped in B-type ultrasonography-proven NAFLD patients, with (n = 246) or without (n = 247) CAD and in healthy controls (n = 304). Serum lipid profiles were determined using biochemical methods. Statistical analyses were performed using SPSS 17.0 statistical software. RESULTS:There were significant differences in the Adrs266729 G allele between the NAFLD patients with and without CAD (P < 0.05). In addition, there was a significant difference in the Adrs2241766 G allele of the NAFLD patients compared with that of the controls (P < 0.05). In the NAFLD CAD population, carriers of the G allele of Adrs266729 had higher serum triglycerides (TG), total cholesterol (TC), fasting plasma glucose (FPG), and low-density lipoprotein (LDL) levels and a lower Ad level than their noncarrier counterparts (P = 0.031, P = 0.034, P = 0.007, P < 0.001, and P < 0.001, respectively). NAFLD patients without CAD had higher TG and serum FPG values and a lower Ad level than their noncarrier counterparts (P = 0.014, P = 0.038, and P < 0.001, respectively). In the NAFLD patients with/without CAD, the carriers of the G allele of Adrs2241766 had higher TG levels (P = 0.039 and P = 0.042, respectively) than those of their noncarrier counterparts. CONCLUSIONS:In this Northern Chinese Han population, the Adrs266729 and rs2241766 G alleles were closely associated with the occurrence of NAFLD. However, only NAFLD patients who carried the Adrs266729 G allele had an increased risk of developing CAD.
Project description:Background and Aims: Accumulated studies have evaluated the effects of glucokinase regulatory protein (GCKR) gene polymorphisms on the risk of nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD), but the association of GCKR polymorphisms with the risk of NAFLD and CAD in the Chinese Han population have remained unclear. The aim of this study was to investigate the association between GCKR gene polymorphisms (rs780094 and rs1260326) and the risk of NAFLD and CAD in NAFLD patients in a Chinese Northern Han population. Methods: GCKR rs780094 and rs1260326 gene polymorphisms were genotyped by polymerase chain reaction sequencing for B-type ultrasonography-proven NAFLD patients with (n = 82) or without (n = 142) CAD, and in healthy controls (n = 152). Serum lipid profiles' levels were determined using biochemical methods. Statistical analyses were conducted using SPSS 22.0 statistical software. Results: As the results showed, significant differences in the serum lipid profiles existed between each group. No significant differences were observed in the distributions of genotypes and alleles of GCKR rs780094 and rs1260326 in each group. The GCKR rs780094 T and rs1260326 T allele carriers possessed decreased body mass index value, and serum fasting plasma glucose and TG levels in the overall subjects, respectively. In addition, the GCKR rs780094 T allele carriers possessed decreased serum fasting plasma glucose level in the controls and NAFLD + CAD patients. Conclusions: GCKR rs780094 and rs1260326 polymorphisms were found to be not associated with the risk of NAFLD nor of CAD in NAFLD patients in this Chinese Northern Han population. GCKR rs780094 T and rs1260326 T alleles could affect the body mass index value and serum fasting plasma glucose and triglyceride levels.
Project description:Little is known about the association of the FADS1/FADS2 SNPs and serum lipid levels and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese southern population. The present study aimed to determine such association in the Chinese southern population. A total of 1,669 unrelated subjects (CAD, 534; IS, 553; and healthy controls, 582) were recruited in the study. Genotypes of the FADS1 rs174546 SNP and the FADS2 rs174601 SNP were determined by the SNaPshot Multiplex Kit. The T allele and TT genotype frequencies of the two SNPs were predominant in our study population. The T alleles were associated with increased risk of CAD and IS. Correspondingly, the C alleles were associated with reduced risk of CAD and IS. Haplotype analyses showed that the haplotype of T-T (rs174546-rs174601) was associated with an increased risk for IS, and the haplotype of C-C (rs174546-rs174601) was associated with a reduced risk for CAD and IS. The two SNPs were likely to influence serum lipid levels. The T allele carriers of the two SNPs and rs174601 TT genotype were associated with decreased serum HDL-C and ApoAI levels in the patient groups and with an increased risk of CAD and IS. The present study suggests that the FADS1 rs174546 SNP and the FADS2 rs174601 SNP are associated with the risk of CAD and IS, and are likely to influence serum lipid levels. However, further functional studies are needed to clarify how the two SNPs actually affect serum lipid levels and the risk of CAD and IS.
Project description:Delta-5 and delta-6 desaturases (D5D and D6D) are key enzymes in endogenous synthesis of long-chain PUFAs. In this sample of healthy subjects (n = 310), genotypes of single nucleotide polymorphisms (SNPs) rs174537, rs174561, and rs3834458 in the FADS1-FADS2 gene cluster were strongly associated with proportions of LC-PUFAs and desaturase activities estimated in plasma and erythrocytes. Minor allele carriage associated with decreased activities of D5D (FADS1) (5.84 × 10(-19) ≤ P ≤ 4.5 × 10(-18)) and D6D (FADS2) (6.05 × 10(-8) ≤ P ≤ 4.20 × 10(-7)) was accompanied by increased substrate and decreased product proportions (0.05 ≤ P ≤ 2.49 × 10(-16)). The significance of haplotype association with D5D activity (P = 2.19 × 10(-17)) was comparable to that of single SNPs, but haplotype association with D6D activity (P = 3.39 × 10(-28)) was much stronger. In a randomized controlled dietary intervention, increasing eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) intake significantly increased D5D (P = 4.0 × 10(-9)) and decreased D6D activity (P = 9.16 × 10(-6)) after doses of 0.45, 0.9, and 1.8 g/day for six months. Interaction of rs174537 genotype with treatment was a determinant of D5D activity estimated in plasma (P = 0.05). In conclusion, different sites at the FADS1-FADS2 locus appear to influence D5D and D6D activity, and rs174537 genotype interacts with dietary EPA+DHA to modulate D5D.
Project description:<b><i>Background and Aims:</i></b> Coronary artery disease (CAD) is a major cause of morbidity and mortality in patients with non-alcoholic fatty liver disease (NAFLD). Previous studies have suggested that <i>TCF7L2</i> rs7903146 was related to the risk of developing NAFLD but the conclusions are not consistent and no related study has been conducted in Chinese populations. The aim of this study was to investigate the association between <i>TCF7L2</i> rs7903146 and the risk of developing NAFLD and CAD in a Chinese Han population. <b><i>Methods:</i></b> <i>TCF7L2</i> rs7903146 genotypes were measured by the MALDI-TOF-MS from 143 NAFLD patients, 159 CAD patients, 131 NAFLD + CAD patients, and 212 healthy controls. The demographic data and serum lipid profiles of all subjects were collected. The distributions of genotype and allele frequency in each group were also tested. Logistic regression was used to investigate the risk of <i>TCF7L2</i> rs7903146 with NAFLD and CAD. All statistical analyses were conducted using SPSS 23.0. <b><i>Results:</i></b> There were no significant differences in the distributions of <i>TCF7L2</i> rs7903146 genotype and allele frequency in each of the two groups, and the <i>TCF7L2</i> rs7903146 CT + TT genotype did not increase the risk of developing NAFLD, CAD, and NAFLD + CAD. Except for body mass index in the control group, the differences of clinical parameters between the <i>TCF7L2</i> rs7903146 T allele carriers and non-carriers in each group were not significant. In the non-obese group, the <i>TCF7L2</i> rs7903146 CT + TT genotype was a protective factor for the development of NAFLD in the non-obese subjects (odds ratio=0.359, 95% confidence interval: 0.134-0.961, <i>p</i> = 0.041). <b><i>Conclusions:</i></b> <i>TCF7L2</i> rs7903146 was not associated with the risk of developing NAFLD, CAD, and NAFLD + CAD in the Chinese Han population. In the non-obese population, the <i>TCF7L2</i> rs7903146 CT + TT genotype was a protective factor against the development of NAFLD.
Project description:<h4>Background/aims</h4>Nonalcoholic fatty liver disease (NAFLD) is closely related to gut-microbiome. There is a paucity of research on which strains of gut microbiota affect the progression of NAFLD. This study explored the NAFLD-associated microbiome in humans and the role of Lactobacillus in the progression of NAFLD in mice.<h4>Methods</h4>The gut microbiome was analyzed via next-generation sequencing in healthy people (n=37) and NAFLD patients with elevated liver enzymes (n=57). Six-week-old male C57BL/6J mice were separated into six groups (n=10 per group; normal, Western, and four Western diet + strains [109 colony-forming units/g for 8 weeks; L. acidophilus, L. fermentum, L. paracasei, and L. plantarum]). Liver/body weight ratio, liver pathology, serum analysis, and metagenomics in the mice were examined.<h4>Results</h4>Compared to healthy subjects (1.6±4.3), NAFLD patients showed an elevated Firmicutes/Bacteroidetes ratio (25.0±29.0) and a reduced composition of Akkermansia and L. murinus (P<0.05). In the animal experiment, L. acidophilus group was associated with a significant reduction in liver/body weight ratio (5.5±0.4) compared to the Western group (6.2±0.6) (P<0.05). L. acidophilus (41.0±8.6), L. fermentum (44.3±12.6), and L. plantarum (39.0±7.6) groups showed decreased cholesterol levels compared to the Western group (85.7±8.6) (P<0.05). In comparison of steatosis, L. acidophilus (1.9±0.6), L. plantarum (2.4±0.7), and L. paracasei (2.0±0.9) groups showed significant improvement of steatosis compared to the Western group (2.6±0.5) (P<0.05).<h4>Conclusion</h4>Ingestion of Lactobacillus, such as L. acidophilus, L. fermentum, and L. plantarum, ameliorates the progression of nonalcoholic steatosis by lowering cholesterol. The use of Lactobacillus can be considered as a useful strategy for the treatment of NAFLD.
Project description:BACKGROUND: Fatty liver index (FLI) was recently established to predict non-alcoholic fatty liver disease (NAFLD) in general population, which is known to be associated with coronary artery atherosclerotic disease (CAD).This study aims to investigate whether FLI correlates with NAFLD and with newly diagnosed CAD in a special Chinese population who underwent coronary angiography. METHODS: Patients with CAD (n?=?231) and without CAD (n?=?482) as confirmed by coronary angiography were included. Among them, 574 patients underwent B-ultrosonography were divided into NAFLD group (n?=?209) and non-NAFLD group (n?=?365). Correlation between FLI and NAFLD was analyzed using pearson's correlation. The associations between FLI and NAFLD as well as CAD were assessed using logistic regression. The predictive accuracy of FLI for NAFLD was evaluated using receiver operating characteristics (ROC) curve analysis. RESULTS: FLI was significantly higher in NAFLD group (37.10?±?1.95) than in non-NAFLD group (17.70?±?1.04), P?<?0.01. FLI correlated with NAFLD (r?=?0.372, P?<?0.001). The algorithm for FLI had a ROC-AUC of 0.721 (95% CI: 0.678-0.764) in the prediction of NAFLD. Logistic regression analysis showed that FLI was associated with NAFLD (adjusted OR?=?1.038, 95% CI: 1.029-1.047, P?<?0.01). The proportion of patients with CAD did not differ among the groups of FLI???30 (32.3%), 30-60 (31.0%), and ?60 (35.3%). No significant association was found between FLI and CAD (adjusted OR?=?0.992, 95% CI: 0.981-1.003 in men and OR?=?0.987, 95% CI: 0.963-1.012 in women, P?>?0.05). CONCLUSIONS: FLI showed good correlation with NAFLD in patients who underwent coronary angiography, but not with newly diagnosed CAD. This might be underestimated because some patients in non-CAD group may have other underlying cardiovascular diseases.
Project description:Fatty acid (FA) status is associated with the risk of several diet-related diseases. Since postmenopausal women are at increased risk of cardiometabolic disturbances, determinants of FA metabolism should be fully understood in this group. We hypothesize that FA metabolism in postmenopausal Polish women may depend on current macronutrient intake and on fatty acid desaturase (FADS) gene polymorphism. One-hundred-and-twenty-eight postmenopausal women with central obesity were recruited to the study and their dietary intake, FA composition in red blood cells (RBC), and rs174556, rs174561, rs174547, and rs3834458 polymorphism of the FADS gene were analyzed. Higher levels of 18:2n-6t level in RBC were associated with higher protein or fat intake or with lower carbohydrate intake. The minor allele carriers of rs174561 of the fatty acid desaturase 1 (FADS1) gene had 9.7% lower concentration of 20:4n?6 in RBC (p < 0.05), but there were no other associations between other FA in RBC levels and FADS1 or fatty acid desaturase 2 (FADS2) polymorphisms. The mean D5D value was 15.3?17.9% lower in the minor allele carriers of each SNPs. We concluded that protein and carbohydrate intake may be associated with FA concentrations in RBC in centrally obese postmenopausal Polish women. The D5D value may be affected by FADS1 or FADS2 polymorphism.