**3.2 Angiogenic genes**

138 Endometriosis - Basic Concepts and Current Research Trends

genome, most SNPs are found in the non-coding DNA, such as within introns and

A number of polymorphisms in candidate genes have been studied to identify the genes responsible for the etiology of endomeriosis. It was only since 2000, that reports were

Transforming growth factor beta (TGF-β) family members are multi-functional cytokines that play a key role in cellular growth, proliferation, and differentiation (Hsieh YY et al, 2005). It has been shown that an association of endometriosis with TGF-β 1-509 gene polymorphism exists. T homozygote and T allele for TGF-β1 are associated with higher susceptibility to endometriosis. Arg448Gly, a common polymorphism located within nuclear receptor interacting protein 1 (NRIP1) gene, is associated with endometriosis. NRIP1 gene variants, separately or in combinations, might act as predisposing factors for human

A significant linkage on chromosome 10q26 and another region of suggestive linkage on chromosome 20p13 as susceptibility loci, has been associated with endometriosis (Treloar

It has been hypothesized that dysregulation of the normal apoptotic process takes place in the endometrium. One of the apoptotic pathways playing a crucial role in the programmed cell death within the endometrium is the Fas-FasL system. Three polymorphisms within FAS (-1377G>A and -670A>G) and FASL (-843C>T) genes, as susceptibility factors for endometriosis have been analysed. However, the differences in the distribution of the polymorphic variants were not statistically significant (Fernandez,R.M.et.al,2005). The angiotensin I-converting enzyme (ACE) A2350G and A-240T gene polymorphism has been suggested as markers of susceptibility in endometriosis as the genotypes and alleles are associated with higher susceptibility to endometriosis and might be associated with

Endometriosis shows significantly elevated frequency in industrial areas and there is a possible genetic pre-disposition (Kennedy S et al. 2001). The glutathione-S-transferases (GSTs) constitute a family of xenobiotic-detoxifying phase-II enzymes catalyzing the conjugation of glutathione to a variety of electrophilic compounds including polycyclic aromatic hydrocarbons (PAH), which are widely present in the human environment and

Several GSTs are polymorphic and some allelic variants causing enzyme activity impairment are suspected to increase susceptibility to malignancies associated with environmental PAH, particularly colorectal cancer (Strange RC & Fryer AA, 1999). A very small portion of endometriosis develops into cancer later, but endometriosis itself is not a malignant disease. It has many characteristics similar to cancer, for example progressive growth, invasive growth, estrogen-dependent growth, recurrence and a tendency to

published establishing an association of genetic polymorphism with endometriosis.

intergenic sequences.

SA et al, 2005).

**3. Endometriosis and genetic polymorphism** 

endometriosis (CaballeroV, et al., 2005).

endometriosis development ( HseihYY etal, 2005).

**3.1 Environmental toxin genes** 

known to be carcinogenic.

metastasis (van Gorp T et al. 2004).

*Vascular endothelial growth factor (VEGF),* a major mediator of angiogenesis and vascular permeability, is known to play a key role in the pathophysiology of endometriosis.The single nucleotide polymorphisms, -460C>T and +405G>C, in the 5'-untranslated region of the VEGF gene were associated with lower promoter activity, which was significantly less common in women with endometriosis suggesting that the +405G allele may influence the likelihood of a woman developing the disease(Bhanoori M et al, 2005).

A relationship between the *alpha 2-Heremans Schmidt glycoprotein (AHSG)* gene polymorphism and endometriosis has been studied. Women not carrying the AHSG 2 allele were found to have twice the risk of endometriosis there by suggesting an association of endometriosis with the AHSG gene polymorphism in Korean women. (Kim JG et al, 2004).
