Genetic variations of MUC17 are associated with endometriosis development and related infertility.
BACKGROUND
Genetic alterations of mucin genes, such as MUC2 and MUC4, were previously identified to be associated with endometriosis and related infertility. Additionally, gene expression profiling has confirmed MUC17 to be overexpressed in mucinous ovarian carcinoma; however, its associated risk for endometriosis remains unclear. This study was focused on the potential impact of genetic variations in MUC17 on endometriosis development and associated clinical features.


METHODS
The study subjects included 189 female Taiwanese patients with pathology-proven endometriosis and 191 healthy Taiwanese women as controls. Five single-nucleotide polymorphisms (rs4729645, rs10953316, rs74974199, rs4729655, and rs4729656) within the MUC17 gene were selected and genotyped using the Taqman genotyping assay to examine the allele frequency and genotype distributions of MUC17 polymorphisms.


RESULTS
Genotyping revealed that the A allele at rs10953316 in MUC17 was a protective genetic factor in endometriosis development (p = 0.008; OR = 0.53; 95% CI: 0.36-0.79). Genetic variation of rs4729655 protected patients against endometriosis-induced infertility, but was associated with a higher cancer antigen 125 (CA125) level. Base-pairing analysis, called MaxExpect, predicted an additional loop in the mRNA structure caused by rs10953316 polymorphism, possibly influencing ribosome sliding and translation efficiency. Such predictions were confirmed by immunohistochemistry that patients with AA genotype at rs10953316 showed low MUC17 levels in their endometrium, patients with GA genotype showed moderate levels, and strong staining could be found in patients with GG genotype.


CONCLUSIONS
MUC17 polymorphisms are involved in endometriosis development and the associated infertility in the Taiwanese population.
The Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan. s5895150@mail.ncku.edu.tw.|Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan. s5895150@mail.ncku.edu.tw.
Ching-Wen
CW
Yang
Department of Obstetrics and Gynecology, China Medical University, Taichung, Taiwan. changyinyi@hotmail.com.|Institute of Environmental Health, China Medical University, Taichung, Taiwan. changyinyi@hotmail.com.
Cherry Yin-Yi
CY
Chang
Department of Pathology, Taichung Hospital, Taichung, Taiwan. luke_mtlai@yahoo.com.tw.
Ming-Tsung
MT
Lai
School of Medicine, China Medical University, Taichung, Taiwan. huiwencmu@gmail.com.
Hui-Wen
HW
Chang
The Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan. cclu@mail.ncku.edu.tw.|Department of Pathology, Medical College, National Cheng Kung University, Tainan, Taiwan. cclu@mail.ncku.edu.tw.
Cheng-Chan
CC
Lu
Human Genetic Center, China Medical University Hospital, Taichung, Taiwan. yichen789@gmail.com.
Yi
Y
Chen
Human Genetic Center, China Medical University Hospital, Taichung, Taiwan. t6783@mail.cmuh.org.tw.
Chih-Mei
CM
Chen
Collage of Medical Science and Technology, Chung Shan Medical University, Taichung, Taiwan. sclee@mercury.csmu.edu.tw.
Shan-Chih
SC
Lee
Human Genetic Center, China Medical University Hospital, Taichung, Taiwan. starbottle0102@hotmail.com.
Pei-Wen
PW
Tsai
Human Genetic Center, China Medical University Hospital, Taichung, Taiwan. yangsh119@hotmail.com.
Su-Han
SH
Yang
Department of Pathology, Kaohsiung University Hospital, Kaohsiung, Taiwan. chlathelas@gmail.com.
Chih-Hung
CH
Lin
Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan. jimsheu@mail.nsysu.edu.tw.|Human Genetic Center, China Medical University Hospital, Taichung, Taiwan. jimsheu@mail.nsysu.edu.tw.|School of Chinese Medicine, China Medical University, Taichung, Taiwan. jimsheu@mail.nsysu.edu.tw.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan. jimsheu@mail.nsysu.edu.tw.
Jim Jinn-Chyuan
JJ
Sheu
Human Genetic Center, China Medical University Hospital, Taichung, Taiwan. d0704@mail.cmuh.org.tw.|School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan. d0704@mail.cmuh.org.tw.
Fuu-Jen
FJ
Tsai
D004715:Endometriosis / Q000150:complications* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D060005:Genotyping Techniques; D006801:Humans; D007150:Immunohistochemistry; D007247:Infertility, Female / Q000209:etiology*; D009077:Mucins / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013624:Taiwan
C450720:MUC17 protein, human; D009077:Mucins