The importance of the UGT1A1 variants in the development of osteopenia and osteoporosis in postmenopausal women

The UDP-glucuronosyltransferase 1A1 (UGT1A1) is involved in the process of estrogen conjugation and elimination. The aim of the study was to analyze whether the UGT1A1 genetic variants are associated with the development of osteopenia and osteoporosis in postmenopausal women. The analysis of the rs4148323 (UGT1A1*6) and rs3064744 (UGT1A1*28) variants in the UGT1A1 gene was conducted using real-time PCR. A significant correlation was observed between the genotypes of the rs3064744 (UGT1A1*28) sequence variant and body mass in women with osteoporosis. The analysis of the Z-score values revealed that women with osteoporosis and carrying the 6/6 variant had the lowest Z-score values as compared to women with the 6/7 and the 7/7 variants (− 1.966 ± 0.242 vs. − 1.577 ± 0.125 and − 1.839 ± 0.233). In addition, the odds ratio for the investigated genotypes (6/6, 6/7, 7/7) indicated an increased risk for osteopenia and osteoporosis in women with the 7/7 homozygous genotype. The analysis of the frequencies of the GG, GA and AA genotypes of the rs4148323 UGT1A1 gene showed no statistically significant differences between the groups. Our analysis revealed that the UGT1A1 rs3064744 variant may affect the risk of developing osteoporosis in postmenopausal Polish women. The UGT1A1 rs4148323 variant is not directly associated with the development of osteopenia and osteoporosis.

Evolutionary history of mammalian UDP-glucuronosyltransferase (UGT)1 and UGT2 families: the emergence of UGT2B subfamily in eutherians after the diversification of flowering plants

The UDP-glucuronosyltransferase (UGT) gene family is responsible for the transfer of glucuronic acid to exogenous and endogenous chemicals. Based on the highly diversified number of genes, the mammalian UGT1A and UGT2B subfamily genes are believed to be involved in the conjugation reactions of xenobiotic metabolism. However, it is speculated that the UGT2 family genes are not involved in the xenobiotic metabolism of avian species due to the less diverse number of genes. In this study, we aimed to investigate the evolutionary history of mammalian UGT1 and UGT2 family genes and determine when the diversification of UGT2B genes occurred. We also attempted to identify the main factors responsible for the diversification of UGT genes. By examining the genomic information and feeding habits of 67 species representing each mammalian family, we discovered that the UGT2B genes emerged in the Eutheria on or after Cretaceous period and that their number were higher in plant-eating mammals (herbivore or omnivore) than in carnivorous mammals. We also found that the UGT2B genes in some herbivorous mammals underwent positive selection. In contrast, the diversity of the UGT1 family genes was inherited from the common ancestor of birds and mammals. Thus, our findings suggest that the emergence of angiosperms (flowering plants) and the occurrence of “animal–plant warfare” influenced the evolution of this gene family involved in the xenobiotic metabolism of eutherians. Furthermore, future research investigating the marsupials and birds that do not possess UGT2B genes is required to elucidate the mechanisms underlying the metabolism of chemical substances in these species.