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The cuttable C-related genotype and allele for the E-cadherin 3 '-UTR Pml I polymorphism are associated with higher susceptibility to endometriosis
(2005-12-01)
Hsieh, Yao-Yuan
;
Chang, Chi-Chen
;
Tsai, Fuu-Jen
;
Hsu, Chin-Moo
;
Lin, Cheng-Chieh
Epithelial cadherin (E-cadherin; CDH1) may influence pericellular proteolysis and intracellular signal transduction, which plays an essential part of tumor invasion. In our study we investigated the correlation between CDH1 gene polymorphism and endometriosis in two groups of pre-menopausal Taiwanese women, group 1 (n = 150) consisting of women with severe stage IV enclometriosis and group 2 (n = 159) of women with no enclometriosis. The polymerase chain reaction (PCR) was used to identify the cuttable (C) and uncuttable (T) polymorphism of the CDH1-Pm/ l gene (rs1801026) located on the T-untranslated region (3'-UTR) of chromosome 16 and compare the genotypes and allelic frequencies of this gene in both groups. We found that the genotype and allele distributions of the CDH1-Pml/ l C/T polymorphism were significantly different in both groups. In group 1 the CDH1*C frequency was 47.7% and the T frequency 52.3%, while the CC homozygote frequency was 6.7%, the TT homozygote 11.3% and the CT heterozygote 82%. In group 2 the CDH1*C frequency was 17% and the T frequency 83%, while the CC frequency was 0.6%, the TT 66.1% and the CT 33.3%. These data indicate that the CDH1 gene polymorphism may be associated with the development of severe endometriosis and that the CDH1 gene C allele is related to higher susceptibility to enclometriosis.
Interleukin (IL)-12 receptor beta 1 codon 378 G homozygote and allele, but not IL-1 (beta-511 promoter, 3953 exon 5, receptor antagonist), IL-2 114, IL-4-590 intron 3, IL-8 3 '-UTR 2767, and IL-18 105, are associated with higher susceptibility to leiomyoma
(2007-04-01)
Hsieh, Yao-Yuan
;
Chang, Chi-Chen
;
Tsai, Chang-Hai
;
Lin, Cheng-Chieh
;
Tsai, Fuu-Jen
Objective: To investigate whether certain polymorphisms are correlated with leiomyoma susceptibility, i.e., interleukin (IL)-1, IL-2, IL-4, IL-8, IL-12, and IL-18, which are all immunomodulatory cytokines that play important roles in host immune responses against cancers. Setting: Departments of gynecology and genetics in a medical center. Patient(s): Women were divided into: [1] a leiomyoma group (n = 162) and [2] a nonleiomyoma group (n = 156). Intervention(s): Genotyping for the IL-1 beta-511 promoter, IL-1 beta exon 5, IL-1Ra, IL-2 114, IL-4 -590 intron 3, IL-8 3'-UTR 2767, IL-12R beta 1 codon 378, and IL-18 105 were evaluated by polymerase chain reaction-restriction fragment length polymorphism. Main Outcome Measurement(s): Genotypes and allelic frequencies in both groups were compared. Result(s): Proportions of IL-12R beta 1 codon 378 *CC/CG/GG in the leiomyoma and nonleiomyoma groups were: [1] 7.4%/43.8%/48.8% and [2] 11.5%/54.5%/34%, respectively. Distributions of other polymorphisms in both groups were not significantly different. Proportions of IL-1 beta-511 promoter *CC/CT/TT were: [1] 22.8%/50%/ 27.2% and [2] 21.8%/57.1%/21.1% in the leiomyoma and nonleiomyoma groups, respectively. The IL-1 beta exon 5 *E1 homozygote/heterozygote/E2 homozygote were: [1] 96.3%/3.7%/0% and [2] 96.9%/3.1%/0% in the leiomyoma and nonleiomyoma groups, respectively. Alleles I/II/III/IV/V for IL-1Ra were: [1] 92.6%/7.1%/0.3%/ 0/0% and [2] 93.9%/5.7%/0%/0.4/0% in the leiomyoma and nonleiomyoma groups, respectively. The IL-2 114 G homozygote/heterozygote/T homozygote were: [1] 27.8%/49.4%/22.8% and [2] 20.5%/53.2%/26.3% in the leiomyoma and nonleiomyoma groups, respectively. The IL-4 -590 intron 3 *RP1 homozygote/heterozygote/ RP2 homozygote were: [1] 64.8%/32.7%/2.5% and [2] 69.2%/26.9%/3.9% in the leiomyoma and nonleiomyoma groups, respectively. The IL-8 3'-UTR 2767 A homozygote/heterozygote/G homozygote were: [1] 14.2%/ 43.8%/42% and [2] 20.5%/41.7%/37.8% in the leiomyoma and nonleiomyoma groups, respectively. The IL-18 *AA/AC/CC were: [1] 56.8%/40.7%/2.5% and [2] 59%/39.7%/1.3% in the leiomyoma and nonleiomyoma groups, respectively. Conclusion(s): The IL-12R beta 1 codon 378 *G homozygote and G allele are related to a higher susceptibility to leiomyoma. The IL-1 beta-511 promoter, IL-1 beta exon 5, and IL-1Ra, IL-2 114, IL-4 -590 intron 3, IL-8 3'-UTR 2767, and IL-18 105 gene polymorphisms are not correlated with the development of leiomyoma.
Angiotensin I-Converting enzyme insertion-related genotypes and allele are associated with higher susceptibility of endometriosis and leiomyoma
(2007-07-01)
Hsieh, Yao-Yuan
;
Lee, Cheng-Chun
;
Chang, Chi-Chen
;
Wang, Yu-Kuo
;
Yeh, Lian-Shun
Endometriosis and leiomyoma display features similar to malignancy, requiring neovascularization to proliferation and growth. Altered vascular-related genes might be related to the development of endometriosis and leiomyoma. Polymorphisms of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) genes have been linked with some vascular diseases. This study investigates whether ACE I/D gene polymorphisms could be used as markers of susceptibility in endometriosis and leiomyoma. Women were divided into three groups: (4) endometriosis (n = 125); (2) leiomyoma (n = 120); () normal controls (n = 128). Genomic DNA was obtained from peripheral leukocyte. ACE I/D gene polymorphisms in intron 16 were amplified by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) Genotypes and allelic frequencies in both groups were compared. We observed the genotype distribution and allele frequency of ACE I/ D gene polymorphisms in both groups were significantly different. Proportions of ACE(star)I homozygote/ heterozygote/D homozygote in both groups were: (1) 50.4/24/25.6%; (2) 25/23.33/51.67%; (3) 10.2/ 29.7/60.1%. Proportions of I/D alleles in each group Were: (1) 62.4/37.6%; (2) 36.7/63.3%; (3) 25/75%. We concluded that ACE(star)I/D gene polymorphisms are associated with endometriosis and leiomyoma suspeptibilities. ACE(star)I-related genotypes and allele are strongly related to the occurrence of endometriosis and moderately related to the occurrence of leiomyoma.
XRCC4 codon 247*A and XRCC4 promoter-1394*T related genotypes but not XRCC4 intron 3 gene polymorphism are associated with higher susceptibility for endometriosis
(2008-05-01)
Hsieh, Yao-Yuan
;
Bau, Da-Tian
;
Chang, Chi-Chen
;
Tsai, Chang-Hai
;
Chen, Chih-Ping
DNA repair systems act to maintain genome integrity in the face of replication errors, environmental insults, and the cumulative effects of age. Genetic variants in DNA repair genes such as X-ray repair cross-complementing group 4 (XRCC4) might influence the ability to repair damaged DNA. Herein we aimed to investigate whether some XRCC4-related polymorphisms were associated with endometriosis susceptibility. Women were divided: (1) severe endometriosis (rAFS stage IV, n = 136) and (2) nonendometriosis groups (n = 112). The polymorphisms of XRCC4 codon 247, XRCC4 promoter - 1394, and XRCC4 intron 3 insertion/deletion (I/D) polymorphism were amplified by PCR and detected by electrophoresis after restriction enzyme (BBS I, Hinc II) digestions. Genotypes and allelic frequencies in both groups were compared. We observed that XRCC4 codon 247*A and XRCC4 promoter - 1394*T related genotypes, but not XRCC4 intron 3 I/D polymorphism, are associated with higher susceptibility for endometriosis. Distributions of XRCC4 codon 247*C homozygote/heterozygote/A homozygote, and C/A allele in both groups were: (1) 89/9.5/1.5% and 93.7/6.3%; (2) 97.3/2.7/0%, and 98.7/1.3% (P < 0.05). Proportions of XRCC4 promoter -1394*T homozygote/heterozygote/G homozygote and T/Gallelein both groups were: (1) 94.1/5.2/0.7% and 96.7/3.3%, and (2) 79.4/17.9/2.7% and 88.4/11.6% (P < 0.005). Proportions of XRCC4*1 homozygote/heterozygote/D homozygote and A/C allele in both groups were: (1) 67.6/30.9/1.5% and 83.2/16.8%, and (2) 70.5/24.1/5.4% and 82.6/17.4% (nondifference). We conclude that XRCC4 codon 247*A and XRCC4 promoter -1394*T related genotypes and alleles, but not XRCC4 intron 3 I/D polymorphism, might be associated with endometriosis susceptibilities and pathogenesis.
T allele for VEGF-460 gene polymorphism at 5 '-untranslated region is associated with higher susceptibility of leiomyoma
(2008-06-01)
Hsieh, Yao-Yuan
;
Chang, Chi-Chen
;
Tsai, Fuu-Jen
;
Lin, Cheng-Chieh
;
Tsai, Chang-Hai
Vascular endothelial growth factor (VEGF) is a regulator of angiogenesis and a mediator of sex steroid-induced cell growth and differentiation. We aimed to investigate if VEGF gene 5'-UTR -460 polymorphism could be used as markers of susceptibility in leiomyoma. Women were divided into two groups: (1) leiomyoma (n=159); (2) nonleiomyoma groups (n=131). VEGF gene-460 polymorphism were detected by polymerase chain reaction and BstUI restriction enzyme analysis. Genotypes and allelic frequencies between both groups were compared. We noted that the proportions of different VEGF polymorphisms in both groups were significantly different. Proportions of cuttable (C) homozygote/heterozygote/uncuttable (T) homozygote for VEGF in both groups were: (1) 0/32/68% and (2) 0/63/37%. Higher percentage of T homozygote and T allele presented in the leiomyoma population. Proportions of C/T alleles in both groups were: (1) 16/84% and (2) 32/68%. We concluded that T homozygotes and T allele of VEGF gene-460 polymorphism are associated with higher risk of leiomyoma development. Heterozygotes and C allele are related with lower risk of leiomyoma formation VEGF gene polymorphism likely contributes to the pathogenesis of leiomyoma.
Insulin-like Growth Factors II exon 9 and E-cadherin-Pml I but not Myeloperoxidase Promoter-463, Urokinase-ApaL I nor Xeroderma Pigmentosum Polymorphisms Are Associated with Higher Susceptibility to Leiomyoma
(2010-06-01)
Hsieh, Yao-Yuan
;
Chang, Chi-Chen
;
Wang, Yu-Kuo
;
Hsu, Kung-Hao
;
Chen, Chih-Ping
Objectives: To investigate the roles of insulin-like growth factor II (IGF2), myeloperoxidase (MPO), E-cadherin (CDH1), urokinase and xeroderma pigmentosum group A and D (XPA, XPD) polymorphisms upon leiomyoma susceptibility. Study Design: Women were divided into: group I, leiomyoma (n=158); group 2, non-leiomyoma (n=156). Polymorphisms (IGF2 exon 9*A/G, MPO-463*A/G, CDH1-Pml I, urokinase-ApaL, XPA*A-23G, XPD*Lys751Gln) were amplified by polymerase chain reaction and detected by electrophoresis after restriction enzyme digestion. Genotype and allelic frequencies were compared between both groups. Results: Associations between leiomyoma with IGF2 and CDH1 polymorphism exist. Proportions of IGF2 exon 9*AA/AG/GG in and CDH1* CC/CT/TT in the groups were: group I, 38/39.2/22.8% and 27.8/66.5/5.7%; group 2, 22.4/53.9/23.7% and 21.2/64.1/14.7. MPO, urokinase, XPA and XPD in both groups were non-significantly different. Proportions of MPO*AA/AG/GG, urokinase*CC/CT/TT, XPA*AA/AG/GG and XPD*AA/AC/CC were: group 1: 1.9/23.4/74.7%, 0.6/7/92.4%, 20.9/55.1/24%, 85.4/14.6/0%; group 2: 3.8/24.4/71.8%, 1.3/4.5/94.2%, 22.4/53.9/23.7%, 84.6/15.4/0%. Conclusion: IGF2*A allele and CDH1*C allele were correlated with leiomyoma susceptibility, which may be associated with leiomyoma development. MPO, urokinase, XPA and XPD polymorphisms are not related to leiomyoma susceptibilities.

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