MedWire News: Through its effect on the rate of estrogen catabolism, the Val432Leu polymorphism of the CYP1B1 gene (CYP1B1) may represent a possible genetic risk factor for osteoporosis in US women, research suggests.
Polymorphisms in the cytochrome P450 genes that encode enzymes for estrogen metabolism are linked to hormone-related cancers, but few studies have investigated links with osteoporosis, note Reina Armamento-Villareal (Washington University School of Medicine, St Louis, Missouri, USA) and co-investigators.
Therefore, Armamento-Villareal and team investigated the impact of two polymorphisms in CYP1B1, reportedly associated with hormone-related cancers, on estrogen metabolism and bone mineral density (BMD), in women from different ethnic backgrounds.
The researchers measured BMD and genotyped the Val432Leu (rs1056836) and Ala119Ser (rs1056827) polymorphisms of CYP1B1 in 220 Caucasian postmenopausal women from St Louis, USA (mean age, 63.5 years) and in 248 women from Palermo, Italy (mean age, 72.9 years).
In addition, urinary estrogen metabolites, serum estradiol, and serum sex hormone-binding globulin levels were measured in the US women only.
As reported in the journal Bone, US women carrying the Leu allele at Val432Leu had significantly higher levels of total urinary estrogen metabolite and significantly lower BMD at the lumbar spine and femoral neck than women with the Val/Val genotype.
In contrast, neither urinary metabolites nor BMD measured in the US women were associated with the Ala119Ser polymorphism in CYP1B1.
A separate analysis of the Italian women revealed that BMD was not associated with either of the polymorphisms investigated.
Of note, the frequencies of both polymorphisms in the US women were in agreement with the Hardy–Weinberg equilibrium, whereas those for the Italian women were not.
Armamento-Villareal et al conclude, “US women with the Leu allele for the CYP1B1 Val432leu polymorphism have increased estrogen catabolism, as indicated by higher urinary estrogen metabolites, compared to those with Val/Val genotype.”
“This may lead to relative hypo-estrogenism and lower BMD in the lumbar spine and femoral neck in these women,” they add.
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