A non-synonymous coding change in the CYP19A1 gene Arg264Cys (rs700519) does not affect circulating estradiol, bone structure or fracture

Abstract

BackgroundThe biosynthesis of estrogens from androgens is catalyzed by aromatase P450 enzyme, coded by the CYP19A1 gene on chromosome 15q21.2. Genetic variation within the CYP19A1 gene sequence has been shown to alter the function of the enzyme. The aim of this study is to investigate whether a non-synonymous Arg264Cys (rs700519) single nucleotide polymorphism (SNP) is associated with altered levels of circulating estradiol, areal bone mineral density or fracture.MethodsThis population- based study of 1,022 elderly Caucasian women (mean age 74.95 ± 2.60 years) was genotyped for the rs700519 SNP were analyzed to detect any association with endocrine and bone phenotypes.ResultsThe genotype frequencies were 997 wildtype (97.6%), 24 heterozygous (2.3%) and 1 homozygous (0.1%). When individuals were grouped by genotype, there was no association between the polymorphism and serum estradiol (wildtype 27.5 ± 16.0; variants 31.2 ± 18.4, P = 0.27). There was also no association seen on hip bone mineral density (wildtype 0.81 ± 0.12; 0.84 ± 0.14 for variants, P = 0.48) or femoral neck bone mineral density (0.69 ± 0.10 for wildtype; 0.70 ± 0.12 for variants, P = 0.54) before or after correction of the data with age, height, weight and calcium therapy. There were also no associations with quantitative ultrasound measures of bone structure (broadband ultrasound attenuation, speed of sound and average stiffness).ConclusionsIn a cohort of 1,022 elderly Western Australian women, the presence of Arg264Cys (rs700519) polymorphism was not found to be associated with serum estradiol, bone structure or phenotypes.

The sex-specific associations of the aromatase gene with Alzheimer’s disease and its interaction with IL10 in the Epistasis Project

“…However, rs700519 does not affect serum estrogen concentration in postmenopausal women. 74 In summary, we have replicated the epistatic interaction between IL10 and CYP19A1 polymorphisms, which increases the risk of AD. Furthermore, we have identified a sex-specific effect limited to females.…”

Genetic Polymorphisms in Estrogen-Related Genes and the Risk of Breast Cancer among Han Chinese Women

“…It is particularly worth noting that the association of rs700519 and rs2069522 was only observed for heterozygotes, but not for homozygotes. One possibility is that the number of rare homozygotes for these two SNPs is too small to show significant evidence, which is consistent with the HapMap database and other reports [41,43]. Furthermore, the biological function of these two SNPs has not been clarified fully.…”

Impact of R264C and R264H polymorphisms in human aromatase function

“…Despite both the mutations occurring on R264 are classified as aromatase single nucleotide polymorphisms [18], no literature data are so far available regarding the R264H substitution. On the contrary, several and discordant are the literature reports about the R264C polymorphism [12,26,28,30,32].…”

“…In contrast, in 2005 it was assessed that the activity of aromatase transfected in COS-1 cells was reduced when cysteine is present in position 264 [26]. It was reported that the missense coding change R264C did not affect the concentration of serum estradiol in Australian women [32], while in Chinese women a case-control study evidenced that this aromatase SNP had no influence in endometrial cancer risk [12].…”