Genotyping of the UDP-glucuronosyltransferase (UGT) 1A7 gene revisited.

Readers are encouraged to write letters to the editor concerning articles that have been published in GASTROENTEROLOGY. Letters that include original, unpublished data will not be considered. Letters should be typewritten and submitted electronically to In 2001 and in 2003, we published 2 studies reporting the role of single nucleotide polymorphisms (SNPs) of the mu-tagen detoxifying UDP glucuronosyltransferase (UGT) 1A7 gene in hepatocellular carcinoma (HCC) 1 and chronic pan-creatitis and pancreatic cancer, 2 concluding that a low catalytic activity variant of UGT1A7 (UGT1A7*3) represents a risk factor for these diseases. In the first paper, 1 59 patients with HCC were compared with 70 controls regarding their UGT1A7 genotype (reported in Table 3 and Figure 3 of that paper). The genotyping data in Table 3 show a deviation from Hardy-Weinberg equilibrium (HWE). Although the observed frequency, for example, of UGT1A7*3/*3 was 10% in controls and 14% in HCC the expected frequency would have been 2.5% (4-fold lower) in controls and 19.4% (1.4-fold higher) in HCC, assuming HWE. Genotyping was conducted by using a single cDNA fragment derived from polymerase chain reaction (PCR) amplification of genomic patient DNA with a UGT1A7 first exon specific primer located from base pair Ϫ61 to Ϫ38 upstream of the ATG start codon (5=-gcggctcgagccacttactatattatag-gagct-3=). The subsequent sequencing analysis and temperature gradient electrophoresis analysis were performed with this fragment. In 2004, after publication of our study in 2001, we identified a separate SNP at position Ϫ57 (Ϫ57 TϾG) in the non-coding region of UGT1A7, which co-localizes with the above specified amplification primer. 3 This coincidence , unknown at the time, is a possible explanation for a PCR amplification bias, and the observed deviation from HWE in our reported genotyping data, and has led us to change our genotyping methodology. Although the data in Table 3 are reproducible with the same methodology, by using a different method (taqMan allelic discrimination analysis) that avoids an influence of Ϫ57GϾC, different results were obtained. In an expanded collective of 125 HCC and 107 controls containing the originally analyzed cohort, allelic frequencies showed (con-Since publication of this study Tseng et al 4 described UGT1A7 SNPs as a risk factor for HCC and an earlier onset of HCC in males, Stucker et al 5 reported an association with a viral etiology of HCC but not in alcohol-related HCC, and Kong et al 6 described an association with HCC risk in hepatitis B carriers. In …