Association of the ESR1 polymorphism with menopause and MLXIPL genetic variant influence serum uric acid levels in Slovak midlife women

Abstract

Objective: This study examines associations between the ESR1 (XbaI, PvuII) and the MLXIPL (rs3812316) gene polymorphisms, and uric acid (UA) levels in Slovak midlife women, subdivided according to their menopause status. Methods: We assessed a total of 362 women from 38 to 65 years of age. Women were recruited from different localities in the western and middle parts of Slovakia. Participants were interviewed during their medical examination at local health centers. They were investigated with respect to a variety of aspects such as medical, anthropometrical, and lifestyle. Participants provided a blood sample for biochemical analyses and DNA genotyping. The MLXIPL gene (rs3812316 SNP variant) and ESR1 gene (PvuII and XbaI) genotypes were then detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Data were analyzed using general linear models and multiple linear regression analyses to adjust for risk factors elevating the UA level such as fat mass (FM), triglycerides (TGs) and creatinine. Results: A positive association between MLXIPL and UA level was observed in the total sample of women after control for confounding covariates, including FM, TGs, and creatinine (P = 0.027). Women with the CC genotype had higher UA levels than the G-allele carriers (261.5 μmol/L ± 68.3 vs 241.1 μmol/L ± 55.1 P = 0.013). A statistically significant association was noticed between postmenopause status and the ESR1 XbaI genotype and their effect on UA (P = 0.028). The Bonferroni pairwise comparison determined that the G-allele carriers in the postmenopausal period had higher estimated UA marginal mean (269.7 μmol/L) than the AA-allele postmenopausal women (236.5 μmol/L) (P = 0.012). The estimated UA marginal mean showed a significant increasing trend according to the MS in G allele carriers (248.5 μmol/L in pre/peri-menopausal vs 269.7 μmol/L in postmenopausal, P = 0.009). In contrast, a decreasing trend was observed in AA carriers (250.6 μmol/L in pre/perimenopausal women vs 236.5 μmol/L in postmenopausal). However, this trend was not statistically significant (P = 0.288). Conclusions: This cross-sectional study suggests that MLXIPL (rs3812316) polymorphism is associated with higher serum UA levels and that the ESR1 (XbaI) polymorphism is associated with UA levels only in the postmenopausal cohort.

Burden of Mendelian disorders in a large Middle Eastern biobank

“…Notably, CK and myoglobin are known to be correlated biomarkers. As for rs782312718 in MLXIPL gene, a cross-sectional study demonstrated an association between this gene and levels of serum uric acid [ 69 ]. All 5 homozygotes for this variant have uric acid levels below 5th percentile.…”

Effects of a therapeutic lifestyle modification intervention on cardiometabolic health, sexual functioning and health-related quality of life in perimenopausal Chinese women: protocol for a randomised controlled trial

“…Apart from menopausal symptoms, other female reproductive histories have also been proven independently to be relevant to midlife health and psychosocial well-being. In particular, a history of miscarriage was identified as being associated with worsening sleep quality while the number of parities was relevant to severely depressed mood and lack of enjoyment 20. Other salient female reproductive histories such as the onset age of menarche and breast feeding have been recognised as being significantly associated with cardiovascular risk factors including obesity and obesity-related hypertension 21.…”