rs10046 Polymorphism of CYP19A1 Gene related to Sex Hormone in Female with Acromegaly Iraqi patients

Abstract

Acromegaly is an uncommon disease which progresses slowly and results from a chronical excess of growth hormone (GH), and connected to noticeable morbidity and increased mortality (Abreu et al., 2016). The following increase in insulin-like growth facter1 (IGF-1) is accountable for greatest systemic complications and for the clinical characteristics (comprise arthralgia, soft tissue changes, visceromegaly, and comorbidities comprise, type 2 diabetes, hypertension , carpal tunnel syndrome, and sleep apnea) related with increased mortality. The medical diagnosis, depends on symptoms associated to presence of the mass pituitary gland or excess of GH, is often belated several years due to the slow development of the disease (Capatina and Wass, 2015). Testicles is produce the testosterone hormone that is accountable for the suitable progress of sexual features of male. Testosterone is too important for keeping bone growth, muscle bulk, sexual function, , a sense of well-being and tolerable levels of red blood cells (Xing et al., 2017). The adrenal gland, ovaries , and likewise the placenta through pregnancy produce the estradiol is female sex hormone that is the most essential hormone through a female’s generative years, also is needed for sexual function and generative also having an effect on the health of a different tissues and organs ((Huang et al., 2015). The cytochrome p450 gene (CYP19A1), found on 15q21.2 chromosome, which encodes for the aromatase enzyme, and catalyzes the last step in biosynthesis of estrogen and metabolism that converting testosterone to estradiol (Chen et al., 2008). Aromatase(CYP19A1) expression is controlled via distinct tissue specific promoters in (he bone, placenta, vascular endothelium, breast, adipose tissue, ovary, and brain causing estrogen production in local extragonadal and systemic gonadalovarian. CYP19A1 is located at chromosome 15 and spans about 123 kb in length via criteria of other cytochrome genes that's encoding the CYP19 is unusually significant since it is above 50 kbp .The gene has a number of alternate non-coding first exons that regulate tissue specific expression and nine coding exons (Corbin et al., 1988). The whole aromatase gene extents about 123 kb (Verma et al., 2012) . Thirty -kb 3′-end of the gene embraces nine exons that encode the aromatase enzyme protein, and 93-kbp at 5′-flanking area of this gene embraces one-off (5′-untranslated) first exon and several of tissue specific promoters, this 1 exon is spliced onto a usual splice crossroads like that each Abstract: Testosterone and estradiol have been considered to be male and female sex hormones, respectively. However, testosterone, also plays a critical role in female sexual function. There is an evidence showing that sex hormone is associated with polymorphisms in the 3' untranslated region T>C rs10046 (SNPs) single nucleotide polymorphisms in CYP19A1 gene. Whole blood genomic DNA was extracted to perform genotyping analysis and rs10046 SNP in the CYP19A1gene by using PCR-restriction fragment length polymorphism technique. Serum testosterone and estradiol levels were determined by using method of enzyme immunoassay competition with a final fluorescent detection. Results show that in estradiol level is significantly decreased while testosterone level is significantly increased in female acromegaly patients when contrasted with healthy control groups in both sexes (p≤0.01) and showed high significance in TT ,CC and TC alleles when contrasted with healthy control groups (p≤0.01).