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Mol. Hum. Reprod. Advance Access originally published online on September 14, 2006
Molecular Human Reproduction 2006 12(11):671-676; doi:10.1093/molehr/gal078
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

KRAS variation and risk of endometriosis

Zhen Zhen Zhao1, Dale R. Nyholt2, Lien Le1, Nicholas G. Martin2, Michael R. James2, Susan A. Treloar2 and Grant W. Montgomery1,3

1Molecular Epidemiology Laboratory and 2Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia

3 To whom correspondence should be addressed at: Molecular Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia. E-mail: grant.montgomery{at}qimr.edu.au

Endometriosis is a common gynaecological disease with symptoms of pelvic pain and infertility which affects 7–10% of women in their reproductive years. Activation of an oncogenic allele of Kirsten rat sarcoma viral oncogene homologue (KRAS) in the reproductive tract of mice resulted in the development of endometriosis. We hypothesized that variation in KRAS may influence risk of endometriosis in humans. Thirty tagSNPs spanning a region of 60.7 kb across the KRAS locus were genotyped using iPLEX chemistry on a MALDI-TOF MassARRAY platform in 959 endometriosis cases and 959 unrelated controls, and data were analysed for association with endometriosis. Genotypes were obtained for most individuals with a mean completion rate of 99.1%. We identified six haplotype blocks across the KRAS locus in our sample. There were no significant differences between cases and controls in the frequencies of individual single-nucleotide polymorphisms (SNPs) or haplotypes. We also developed a rapid method to screen for 11 common KRAS and BRAF mutations on the Sequenom MassARRAY system. The assay detected all mutations previously identified by direct sequencing in a panel of positive controls. No germline variants for KRAS or BRAF were detected. Our results demonstrate that any risk of endometriosis in women because of common variation in KRAS must be very small.

Key words: association test/endometriosis/KRAS/polymorphism


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