Metabolic a genomic manner 6. ER belongs

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Metabolic syndrome is a complex of interrelated risk factors for cardiovascular
disease (CVD) and diabetes. These factors

include dysglycemia, raised blood pressure, elevated triglyceride (TG)
levels, decreased high-density lipoprotein cholesterol (HDL-C) levels, and
obesity (particularly central adiposity). The associations and clustering of
these factors have been known for decades. Identification of these risk factors
has clearly demonstrated that the syndrome is common and that it has a rising
prevalence worldwide that relates largely to increasing

obesity and sedentary lifestyles. As a result, metabolic syndrome is
now both a public health and clinical issue 1.

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There is widespread agreement that atherosclerotic cardiovascular disease
(ASCVD) is the major clinical outcome of metabolic syndrome; all the metabolic
risk factors predispose patients to the development of ASCVD 1,2.
Metabolic syndrome is also associated with an elevated risk for type 2 diabetes
3. When diabetes develops, it serves as a powerful risk
factor for the development of ASCVD in and of itself 2. On the
other hand, diet plays an important role in the development of metabolic
syndrome; and a low-fat 4 or fruit and dairy diet 5 is
associated significantly with decreased risk for metabolic syndrome. Estrogen
exerts many protective effects on the cardiovascular system, mainly through
estrogen receptor alpha (ER-?), including direct effects on vascular tissues and
systemic effects. Estrogen can cause vasodilatation through ERs in both a
rapid, non-genomic and a genomic manner 6. ER belongs to the nuclear
hormone receptor superfamily and acts as a ligand-activated transcription
factor 7. The human ESR1 gene is located on the long arm of
chromosome 6 (6q25.1) and contains 8 exons separated by 7 intronic regions 8. Several
polymorphisms of the ESR1 gene, both single nucleotide polymorphisms (SNPs) and
tandem repeats, have been identified. In candidate gene association studies,
the most extensively investigated SNPs of the ESR1 gene have been, XbaI c.454-351 A/G: XbaI
restriction site (rs9340799)
and PvuII c.454-397 T/C: PvuII restriction site (rs2234693),
which are both in the first intron 9. The XbaI and PvuII SNPs of the ESR1 gene were found to be associated
with various diseases and metabolic factors, including cardiovascular disorders
10,11, venous thromboembolism 12,13, abdominal obesity 14, blood pressure 15, lipoprotein
metabolism and serum lipid levels 9. The aim of the current study
was to investigate the association of ESR1 polymorphisms (XbaI and PvuII) with metabolic syndrome and its related phenotypes
in females.

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