Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with high mortality rate. Upstream transcription factor 1 (USF1) is a ubiquitously expressed transcription factor that regulates the expression of genes involving in different biological processes, including cancer. The aim of this study is to examine the correlation between USF1 polymorphisms and HCC susceptibility. Ninety-four HCC patients and 100 healthy volunteers are recruited in our study. Tag single nucleotide polymorphisms (Tag-SNPs) were retrieved in the International HapMap Project Databases. Extraction of genomic DNAs was conducted with TaqMan Blood DNA kits. Genotyping of USF1 polymorphisms were carried out with TaqMan SNPs genotyping assay. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated to evaluate the association between USF1 polymorphisms and HCC risk. All statistical analyses were performed with SPSS 20.0 software. Five tag-SNPs were identified to represent the genetic variants of USF1. Our results suggested that rs2516839 in the 5\'UTR of USF1 was significantly associated with increased HCC risk (AA vs GG: OR = 3.15; 95% CI 1.44-6.87; P = 0.003; GA + AA vs AA: OR = 1.85; 95% CI 1.04-3.30; P = 0.034; AA vs GG + GA: OR = 2.96; 95% CI 1.40-6.26; P = 0.004; A vs G: OR = 2.09; 9% CI 1.35-3.23; P < 0.001). Although rs2073655 in the intron region of USF1 was also shown to be correlated with decreased HCC susceptibility in recessive model (TT vs CC + CT: OR = 0.40; 95% CI 0.54-0.75; P = 0.004), this association was not conclusive. Our results indicated that the SNP of rs2516839 have close association with increased risk of HCC. Further studies may be needed to validate our results and gain insights into the pathological mechanism of USF1 gene in the HCC tumorigenesis.

Hepatocellular carcinoma (HCC) is a prototype of liver cancer, which is closely related to manifested metabolism of lip and glucose. Upstream transcription factor 1 (USF1) is an important transcription factor in human genome, and it regulates the expression of multiple genes associated with lipid and glucose metabolism. This study aims at investigating the correlation between seven common USF1 polymorphisms (i.e., -1994 G>A, -202 G>A, 7998 A>G, -844 C>T, 9042 C>G, 9441 T>C, and -2083 G>A) and the risk of HCC. Elucidation of the interaction might be of vital importance to the diagnosis and prognosis of HCC. One hundred and fifty-five HCC patients and 160 healthy controls from a Chinese Han population were involved in this study. Tag single-nucleotide polymorphisms (SNPs) were identified with reference to CBI-dbSNP and HapMap databases. DNA was extracted from blood samples, and matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was conducted to determine the polymorphisms of USF1. Odds ratio (OR) and 95% confidence interval were applied to evaluate the difference of genotype distribution. Seven SNPs were selected to be representatives. No significant difference was observed concerning -1994 G>A, 7998 A>G, 9042 C>G, 9441 T>C, and -2083 G>A polymorphisms (all P > 0.05). A significantly elevated genotype frequency regarding -202 G>A polymorphism was observed in HCC patients [AA vs. GG: OR 2.13 (1.13-4.01), P = 0.019; AA vs. GG+GA: OR 2.22 (1.32-3.75), P = 0.003; A allele vs. G allele: OR 1.46 (1.07-2.01), P = 0.018]. Subjects carrying mutant -844 C>T genotypes also had a higher risk of HCC [CT vs. CC: OR 1.88 (1.17-3.04), P = 0.009; CT+TT vs. CC: OR 1.83 (1.17-2.86), P = 0.008; T allele vs. C allele: OR 1.49 (1.06-2.09), P = 0.020]. Further studies are recommended to validate our findings in different ethnicity and to clarify the functional relationship between USF1 polymorphisms and the susceptibility of HCC.

Hall et al. (2010) describe a boy with mosaic trisomy of the proximal part of 19q, with obesity, macrocephaly and global developmental delay. The patient is interesting with regard to his cytogenetic abnormality, which is smaller than those previously reported, and does not include the candidate obesity and insulin-resistance genes identified by other authors (Zung et al., 2007; Davidsson et al., 2010) as possible causes of the overweight/obesity seen in four of five previously documented patients. This suggests that a novel obesity locus may reside in the duplicated region 19q13.11–q13.2. We present a phenotypically similar boy with intrachromosomal insertion of material derived from proximal 19q into proximal 19p, causing mosaic trisomy 19q12–q13.2, and consider the role of USF2, a master transcriptional regulator of metabolic genes, in 19q phenotypes.

OBJECTIVE: Upstream transcription factor 1 (USF1) regulates genes of glucose and lipid metabolism. Polymorphisms in the USF1 gene showed association with familial combined hyperlipidemia and lipid parameters. The aim of our study was to examine the associations between USF1 polymorphisms and lipid parameters as well as incident type 2 diabetes mellitus (T2DM) in German Caucasians.
METHODS: We genotyped eight polymorphisms in the USF1 gene in 2067 middle-aged (35-74 years) individuals including 498 incident T2DM cases and 1569 non-cases of the population-based case-cohort study from the MONICA/KORA Augsburg project.
METHODS: Six polymorphisms and their haplotypes were analyzed using multivariable linear regression and Cox proportional hazards models.
RESULTS: Polymorphism rs3737787 was inversely associated with incident T2DM in women with decreased risk for female heterozygotes compared with women homozygous for the major allele (Hazard ratio=0.57; 95% confidence intervals: 0.38-0.87; P=0.008). After correction for multiple testing, significance remained. Polymorphisms rs3813609 and rs1556259 were significantly associated with reduction in low-density lipoprotein (LDL) cholesterol (p(NOM)=0.001; p(NOM)=0.00002) in women. Analyses also indicated associations of haplotypes with LDL cholesterol in women, but the association lost statistical significance after correction for multiple testing. Total serum cholesterol (TC) and high-density lipoprotein (HDL) cholesterol were weakly associated (P<0.05) with USF1 polymorphisms in women. No significant associations were found in men.
CONCLUSIONS: In this large population-based study, statistically significant associations of USF1 polymorphisms with incident T2DM and LDL cholesterol were found in women, but not in men. Genetic variants in the USF1 gene showed weak or no associations with TC and HDL cholesterol.