Dataset Information

FTO Polymorphisms are Associated with Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Susceptibility in the Older Chinese Han Population.

ABSTRACT:

Background

As fat and obesity play a vital role in the pathophysiology of metabolic dysfunction-associated fatty liver disease (MAFLD), this study aims to investigate the association between the fat mass and obesity-associated gene (FTO) and MAFLD.

Methods

Six SNPs (rs6499640, rs1421085, rs8050136, rs3751812, rs9939609 and rs9930506) within FTO were genotyped for 741 MAFLD patients (median age, 69.98; interquartile range, 66.55-75.93) and 825 healthy people (median age, 69.94; interquartile range, 66.39-75.64). Allele and genotype frequencies, pairwise linkage disequilibrium (LD) and haplotype analysis were calculated.

Results

BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, triglyceride, alanine transaminase, glutamyl transpeptidase and the prevalence of diabetes were found to be higher in the MAFLD individuals comparing to the control ones (P < 0.05). For rs1421085, the C allele frequency was remarkably higher in MAFLD after Bonferroni correction (OR [95% CI] =1.353 [1.095-1.671]; P _corr =0.030), and a significantly different genotype result was observed in log-additive model (OR [95% CI] =1.369 [1.108-1.691]; P _corr =0.024). For rs8050136, significantly increased A allele frequency was observed in MAFLD (OR [95% CI] =1.371 [1.109-1.695]; P _corr =0.024), and A-allele carriers showed increased MAFLD risk (OR [95% CI] =1.393 [1.103-1.759]; P _corr =0.030). For rs3751812, the T allele frequency was remarkably higher in MAFLD (OR [95% CI] =1.369 [1.108-1.691]; P _corr =0.024), and T-allele carriers demonstrated high MAFLD risk (OR [95% CI] =1.392 [1.103-1.756]; P _corr =0.030). For rs9939609, A allele frequency was also remarkably high in MAFLD (OR [95% CI] =1.369 [1.108-1.691]; P _corr =0.024), and A-allele carriers were more susceptible to MAFLD (OR [95% CI] =[1.103-1.756]; P _corr =0.030). A strong LD was found among rs1421085, rs8050136, rs3751812 and rs9939609 (r² >0.8), and individuals with C-A-T-A haplotype had an elevated MAFLD risk (P =0.005).

Conclusion

The case-control study indicated that C variant of rs1421085, A variant of rs8050136, T variant of rs3751812 and A variant of rs9939609 are associated with elevated MAFLD risk in the older Chinese Han population.

SUBMITTER: Gu Z

PROVIDER: S-EPMC7429205 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPrevious studies have suggested that fat mass-and obesity-associated (FTO) gene is associated with body mass index (BMI) and the risk of obesity. This study aims to assess the association of five FTO polymorphisms (rs9939609, rs8050136, rs1558902, rs3751812 and rs6499640) with obesity and relative parameters in Han Chinese adolescents.MethodsWe examined a total of 401 adolescents, 223 normal weights (58.7% boys, 41.3% girls), 178 overweight (60.1% boys, 39.9% girls), aging from 14 to 18-years-old, recruited randomly from public schools in the central region of Wuxi, a southern city of China. DNA samples were genotyped for the five polymorphisms by Sequenom Plex MassARRAY. Association of the FTO polymorphisms with BMI, serum fasting plasm glucose (FPG), fasting insulin (FIns), triglyceride (TG) and cholesterol (TC) were investigated.Results1) Serum FPG, FIns, TG and TC were statistically significant higher than that in normal control group. 2) We found that BMI was higher in the rs9939609 TA+AA, rs8050136 AC+AA, rs1558902 TA+AA and rs3751812 GT+TT genotypes than in wild TT genotypes (rs9939609: P = 0.038; rs1558902: P = 0.038;), CC genotypes(rs8050136: P = 0.024) and GG genotypes (rs3751812: P = 0.024), which were not significant on adjusting for multiple testing. 3) In case-control studies, five polymorphisms were not significantly associated with overweight (p>0.05), haplotype analyses showed non-haplotype is significantly associated with a higher risk of being overweight (p>0.05). 4) There existed no significant statistical difference about FPG, FIns, TG and TC in genotype model for any SNP.ConclusionsOur study has conducted a genetic association study of the FTO polymorphisms with BMI, serum fasting plasm glucose (FPG), fasting insulin (FIns), triglyceride (TG) and cholesterol (TC). Our study found BMI of subjects with A allele of FTO rs9939609 is higher than that with T allele. Further studies on other polymorphisms from FTO and increasing the sample size are needed.