Common Variation in the CYP17A1 and IFIT1 Genes on Chromosome 10 Does Not Contribute to the Risk of Endometriosis

Abstract

Endometriosis is a complex disease involving multiple susceptibility genes and environmental factors. Our previous studies on endometriosis identified a region of significant linkage on chromosome 10q. Two biological candidate genes (CYP17A1 and IFIT1) located on chromosome 10q, have previously been implicated in endometriosis and/or uterine function. We hypothesized that variation in CYP17A1 and/or IFIT1 could contribute to the risk of endometriosis and may account for some of the linkage signal on chromosome 10q. We genotyped 17 single nucleotide polymorphisms (SNPs) in the CYP17A1 and IFIT1 genes including SNP rs743572 previously associated with endometriosis in 768 endometriosis cases and 768 unrelated controls. We found no evidence for association between endometriosis and individual SNPs or SNP haplotypes in CYP17A1 and IFIT1. Common variation in these genes does not appear to be a major contributor to endometriosis susceptibility in our Australian sample.

Common variation of the CYP17 gene in Iraqi women with endometriosis disease

“…Also likely to be in strong linkage disequilibrium with each other and with the T to C polymorphism, which is in the promoter region of CYP17 [20]. Strong linkage disequilibrium (LD) was detected between SNP rs743572 and the other two SNPs in the gene (rs6162 and rs6163) in Australian sample [9]. Nichola et al genotyped 10 variants in CYP17 , including rs6163, which is highly correlated with rs743572, the minor (A) allele of rs6163 was associated with a modest reduction in levels of urinary estrone glucuronide and a modest increase in levels of plasma androstenedione in premenopausal women [7].…”

“…Genotyped G/T and C/T of exon 1 (rs6162) and (rs6163) were a highly correlated with (rs743572), the minor allele of (rs6163) was associated with a modest increase in levels of plasma androstenedione in premenopausal women [7], [8]. Genetic studies of CYP17A1 variants to date have followed a defined biological hypothesis suggesting the 5′UTR promoter region (rs743572) is associated with gene expression [9]. To study further a possible role of CYP17A1 in endometriosis, we evaluated the risk of endometriosis in relation to common genetic variation of CYP17A1 and determine the main effects of those variations on the gene expression in a population based case control study conducted in Iraqi women with endometriosis.…”

CYP17A1 rs743572 polymorphism might contribute to endometriosis susceptibility

“…[ 27 ] The positive association has also been discovered by Hsieh et al in a Chinese population, [ 28 ] although other studies indicated that rs743572 SNP was not associated with the risk of endometriosis. [ 29 , 30 ] Meanwhile, no evidence has been found in the meta-analysis for the significant association between rs743572 and endometriosis risk. [ 31 ] These difference might be caused by different populations, relatively small sample size or other factors.…”

Gene Polymorphisms in FAS (Rs3740286 and Rs4064) Are Involved in Endometriosis Development in Brazilian Women, but not those in CASP8 (rs13416436 and rs2037815)

“…Although we have identified an association of polymorphisms in chromosome 10 with susceptibility to endometriosis, another study showed that polymorphisms in the cytochrome P450 family 17 subfamily A member 1 (CYP17A1) and interferon-induced protein with tetratricopeptide repeats 1(IFIT1) genes in chromosome 10 did not contribute to the risk of endometriosis in the Australian population. 28 A systematic literature review conducted in 2008 showed that: 1) there is evidence of genetic linkage to chromosomes 7 and 10; 2) genetic variants in 76 genes were associated with endometriosis; and 3) GWAs are recommended to locate the genetic variants that contribute to a range of common diseases. 29 The present study is limited due to the small sample size, which decreased our ability to solidify statistic associations.…”