**3.3.1 Estrogen Receptor (ER) gene**

The risk and severity of endometriosis has been associated with polymorphisms in genes coding for estradiol-synthesizing enzyme like the Ser312Gly polymorphism in 17-beta-

Genetic Polymorphisms and Molecular Pathogenesis of Endometriosis 141

menstrual cycle is controlled largely by progesterone, and this sex steroid hormone is absolutely required for normal implantation and pregnancy. PROGINS polymorphism of the progesterone receptor may be associated with an increased risk of endometriosis in

Microsatellites are short sequence elements that consist of mononucleotide to hexanucleotide motifs reiterated several times. This form of genomic instability is caused by defects in the DNA mismatch repair system. Genomic instability is an almost universal feature of cancer cells. Microsatellite instability is a DNA level instability seen in a number of tumors, including colon cancers. Instability is probably necessary to enable a cell to amass enough mutations and is not a chance feature, but is the result of selection. High frequency of MSI is defined as >29% of all markers and are defined as a class of MSI positive tumors (Strachanan & Read 2004).

Genetic alterations in microsatellite marker sites among eight tumor suppressor genes in endometriosis were examined and reported that MSI is not ubiquitous in endometriosis and may be uncommon (Nakayama K et al, 2001). MSI assays reveal an allelic imbalance and loss of heterozygosity (LOH) on p16(Ink4), GALT, p53, APOA2 loci in endometriosis. The

Gene expression profiles in endometriosis have been studied by two groups. In one study differentially expressed genes were investigated in epithelial and stromal cells from deep endometriosis and matched eutopic endometrium using cDNA microarrays and laser capture microdissection (Matsuzaki S et al, 2004) while Smith SK , (2003) undertook a genome-wide analysis of transcript abundance and changes in transcript level between normal endometrium in the proliferative and secretory phases of the menstrual cycle, between normal and ectopic endometrium of endometriosis and between normal and RU-

Gene expression profiling to identify genes involved in endometriosis has shown that Cyr61 gene, which codes for cystein-rich heparin-binding protein that promotes cell adhesion, migration and neo-vascularisation was deregulated (Absenger Y et al, 2004). Overexpression of p53 in atypical endometriosis and cancer associated with endometriosis has been reported (Sainz de la Cuesta R et al, 2004). Thymosin beta 4 (Tb4) gene expression, an actin sequestering protein, was up-regulated in uterine adenomyosis(endometriosis of myometrium) in mice ( Kawahara R et al, 2003). Dysregulation of 14 genes was found to be overtly associated with endometriosis by Real- Time RT-PCR expression profiling of

The research work aimed to identify polymorphisms of candidate genes which increase susceptibility to endometriosis by genetic and molecular methods in 106 women who were

9p21 locus may be a prognostic marker of the disease (Goumenou AG et al, 2001).

Italian women (Lattuada et al, 2004).

**4. Microsatellite Instability (MSI)** 

**4.1 Microsatellite (MS) markers** 

**5. Gene expression** 

486 exposed endometrium.

endometriosis (Wei Ping Hu et al, 2006).

**6. Research by our group** 

hydroxysteroid dehydrogenase type 1 (HSD17B1). Evidence for association between the Ser312Gly polymorphism in HSD17B1 and endometriosis was found in a Japanese population. The A-allele of HSD17B1 appears to confer higher risk for endometriosis (Tsuchia M et al, 2005).

The *Alu*I polymorphism in the ERβ gene is associated with an increased risk of stage IV endometriosis in a Japanese population (Wang Z et al, 2004).The *Pvu*II polymorphism of the ERα gene is associated with the risk for endometriosis, adenomyosis and leiomyomata in Japanese women (Kitawaki J et al, 2001). The ERα dinucleotide repeat and cytochrome P450c17α gene polymorphisms are associated with susceptibility to endometriosis in Taiwanese women (Hsieh.Y Y et al, 2005).
