UGT1A1*28 relationship with abnormal total bilirubin levels in chronic hepatitis C patients: Outcomes from a case-control study.

Gilbert syndrome (GS) is a frequent benign clinical condition, marked by intermittent unconjugated hyperbilirubinemia, mostly due to the polymorphism uridine diphosphate-glucuronosyltransferase 1A1*28 (UGT1A1*28). Hyperbilirubinemia has been reported in a GS patient undergoing hepatitis C treatment, and other UGT isoforms polymorphisms have been linked to worse outcomes in viral hepatitis. Yet, little is known to GS contributions' to the liver disease scenario. Our aim was to assess UGT1A1 genotypes' frequency in chronic hepatitis C (CHC) patients and correlate with total bilirubin (TB). This is a case-control study in a large tertiary medical center. Cases were CHC patients confirmed by hepatitis C virus (HCV)-polymerase chain reaction. Exclusion criteria were hepatitis B virus or human immunodeficiency virus (HIV) coinfection. Control were healthy blood donors. UGT1A1 promoter region gene genotyping was performed, and bilirubin serum levels were available for HCV patients. Genotypes and alleles frequencies were similar in case (n = 585; P = 0.101) and control groups (n = 313; P = 0.795). Total bilirubin increase was noticed according to thymine-adenine repeats in genotypes (P < 0.001), and the TB greater than 1 mg/dL group had more UGT1A1*28 subjects than in the group with TB values <1 mg/dL (18.3 vs 5.3; P < 0.001). Bilirubin levels are linked to the studied polymorphisms, and this is the first time that these findings are reported in a chronic liver disease sample. Among patients with increased TB levels, the frequency of UGT1A1*28 is higher than those with normal TB. Personalized care should be considered to GS, regarding either abnormal bilirubin levels or drug metabolism.

Genetic risk for alcoholic chronic pancreatitis.

In recent years many studies have examined the genetic predisposition to pancreatic diseases. Pancreatic disease of an alcoholic etiology was determined to be a multi-factorial disease, where environmental factors interact with the genetic profile of the individual. In this review we discuss the main results from studies examining the frequency of genetic mutations in alcoholic chronic pancreatitis.

Is Gilbert syndrome a new risk factor for breast cancer?

Patients with Gilbert syndrome have an impaired function of the enzyme UGT1A1, responsible for the degradation of 4-OH-estrogens. These elements are produced by the degradation of estrogens and are well-known carcinogens. In theory, patients with Gilbert syndrome accumulate 4-OH-estrogens and, therefore, might have a higher risk for breast cancer, especially when exposed to higher levels of estrogens. If this theory is true, a new risk group for breast cancer would be described, producing new insights in breast carcinogenesis.