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

Anna Bogacz,Daniel Kotrych,Izabela Uzar,Małgorzata Łochyńska,Jarosław Gorący,Adam Kamiński,Agnieszka Seremak-Mrozikiewicz,Bogusław Czerny

doi:10.1038/s41598-021-96429-x

Abstract

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.

Highlights

A better understanding of the molecular mechanisms underlying osteoporosis is vital for the diagnosis and treatment, not to mention the earliest possible identification of the factors predisposing to the development of the disease[5]
The risk of osteoporosis and osteopenia has been linked to genetic variants, especially the COL1A1, VDR, BMP2, TLR genes, as well as the LRP5 gene involved in the Wnt/β-catenin signaling pathway[7,8,9,10,11,12]
The association of the UGT1A1 on the risk of developing osteopenia and osteoporosis was evaluated, which was correlated with the clinical parameters, including bone parameters

Summary

Introduction

A better understanding of the molecular mechanisms underlying osteoporosis is vital for the diagnosis and treatment, not to mention the earliest possible identification of the factors predisposing to the development of the disease[5]. The search for new genes which play an important role in the regulation of bone mass and the development of osteoporosis continues. Previous GWAS studies demonstrated a link between polymorphisms of the genes related to estrogen metabolism and osteoporosis and the risk of bone fracture[12]. Researchers are constantly looking for new genetic variants that could affect the risk of developing osteoporosis. Conducted scientific studies analyze the influence of genetic variants of the UGT1A1, including UGT1A1*6 (211G>A, rs4148323), UGT1A1*27 (686C>A, rs35350960), UGT1A1*60 (− 3263T>A, rs4124874), and TA repeat variation of UGT1A1*28 (A(TA)7TAA, rs3064744) on the risk of developing osteoporosis or other pathological entities, e.g. Gilbert’s Syndrome. The aim of the study was to investigate whether the UGT1A1 rs3064744 (UGT1A1*28) and the rs4148323 (UGT1A1*6) genetic variants are associated with the development of osteopenia and osteoporosis in postmenopausal women

Objectives

Methods

Results

Conclusion