Chi Chen Chang

The proline form of p53 codon 72 polymorphism is associated with endometriosis

OBJECTIVE To evaluate the association between endometriosis and the p53 polymorphism. DESIGN Prospective study. SETTING Department of gynecology and genetics in a medical center. PATIENT(S) Women with and without endometriosis. INTERVENTION(S) Women were categorized as having moderate or severe endometriosis (n = 118) or no endometriosis (n = 140). MAIN OUTCOME MEASURE(S) Polymerase chain reaction was used to detect p53 codon 72 polymorphisms (arginine homozygosity, heterozygosity, and proline homozygosity). Associations between endometriosis and p53 polymorphisms were evaluated. RESULT(S) The distributions of different p53 polymorphisms differed significantly between groups. The respective proportions of arginine homozygotes, heterozygotes, and proline homozygotes were 10.2%, 66.9%, and 22.9% in the group with endometriosis and 30.7%, 50%, and 19.3% in the group without endometriosis. CONCLUSION(S) Endometriosis is associated with p53 polymorphism. p53 arginine homozygotes have lower risk for endometriosis. Heterozygotes and proline homozygotes have higher risk for endometriosis.

Polymorphism for transforming growth factor beta 1-509 (TGF-B1-509): Association with endometriosis

Transforming growth factor beta (TGF-B) family members are multi-functional cytokines that play a key role in cellular growth, proliferation, and differentiation. The aim of the study was to investigate whether the TGF-B1-509 gene polymorphism could be used as a marker of susceptibility in endometriosis. Women were divided into two groups: endometriosis (n = 150) and non-endometriosis (n = 159). Polymorphisms for TGF-B1-509 genes were amplified by polymerase chain reaction and detected after restriction enzyme digestion. Genotypes and allelic frequencies in both groups were compared. Genotype proportions and allele frequencies of TGF-B1 gene polymorphisms differed significantly in both groups. Proportions of C homozygote, heterozygote, and T homozygote for TGF-B1 gene polymorphisms were 9.3/61.3/29.4% in the endometriosis group and 41.3/58.5/0% in the non-endometriosis group. Alleles C and T for TGF-B1 gene polymorphism were 40/60% (endometriosis) and 70.8/29.2% (non-endometriosis). Association of endometriosis with TGF-B1-509 gene polymorphism exists. T homozygote and T allele for TGF-B1 are associated with higher susceptibility to endometriosis.

Prenatal diagnosis of Apert syndrome

Apert syndrome (AS) is clinically characterized by typical facial features and symmetrical syndactyly of the digits. AS is inherited as an autosomal dominant trait. Recently, a fibroblast growth factor receptor 2 (FGFR2) mutation, either C934G or C937G, was identified in exon IIIa. Our report documents an affected mother and son in whom one of the two mutations in AS had occurred sporadically in the mother. The diagnosis of AS was based on associated abnormal physical features and on molecular genetic analysis. A C‐to‐G transversion at position 937 of the cDNA resulting in a proline‐to‐arginine substitution at codon 253 was found in the mother. In her second pregnancy, prenatal diagnosis by both restriction analysis and direct sequencing was undertaken and this showed that the female fetus had not inherited the mutation.

Estrogen receptor thymine-adenine dinucleotide repeat polymorphism is associated with susceptibility to leiomyoma

OBJECTIVE To evaluate the association between leiomyomas and estrogen receptor gene polymorphism. DESIGN Prospective study. SETTING Department of gynecology and genetics. PATIENT(S) Women with (n = 159) or without leiomyomas (n = 131). MAIN OUTCOME MEASURE(S) Polymerase chain reaction was used to detect dinucleotide (thymine-adenine [TA]) repeat polymorphisms upstream of the estrogen receptor gene. Genotypes were classified as A through P according to the number of the TA repeats from 12 to 27. Distributions of TA repeat for estrogen receptor in both groups were compared. RESULT(S) Genotypes A to E were detected in 10.7%, 18.9%, 15.7%, 16.4%, and 4.4%, respectively, of women with leiomyomas and 4.2%, 9.5%, 20.6%, 19.1%, and 10.3% of women without leiomyomas. Women with genotypes A and B (12 or 13 TA repeats) have a higher risk for leiomyomas, and those with genotype E (16 TA repeats) have a lower risk. CONCLUSION(S) Estrogen receptor gene polymorphism probably contributes to the pathogenesis of leiomyoma and may predict the susceptibility to leiomyoma. The 12 and 13 TA repeats are associated with a higher risk 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†

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/G allele in 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*I 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. Mol. Reprod. Dev. 75: 946–951, 2008.

Human lymphocyte antigen B-associated transcript 2, 3, and 5 polymorphisms and haplotypes are associated with susceptibility of Kawasaki disease and coronary artery aneurysm

The correct list of authors and affiliations should read: Yao-Yuan Hsieh, Ying-Ju Lin, Chi-Chen Chang, Da-Yuan Chen, Chin-Mu Hsu, Yu-Kuo Wang, Kung-Hao Hsu, and Fuu-Jen Tsai School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan Division of Infertility Clinic, Hsieh Yao-Yuan Womens’ Hospital, Taichung, Taiwan Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan Department of Medical Research, China Medical University Hospital, Taichung, Taiwan Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan Department of Biological Science and Technology, National Chiao Tung University, Hsin Chu, Taiwan Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University,

Cytochrome P450c17α 5′-untranslated region *T/C polymorphism in endometriosis

Estrogen plays a role in the pathogenesis of endometriosis. The CYP17 gene codes for the cytochrome P450c17α enzyme that is involved in the estrogen biosynthesis. We aimed to investigate if CYP17 polymorphism could be used as marker to predict the susceptibility of endometriosis. Women were divided into two groups: (1) severe endometriosis (n=119); (2) non-endometriosis groups (n=128). A 169-bp fragment encompassing the T/C polymorphic site in 5′-untranslated promoter region (5′-UTR) of the CYP17 was amplified by the polymerase chain reaction, treated with restriction enzyme MspA1I, and electrophoresis. The polymorphism was divided into restriction-enzyme indigestible (T homozygote), T/C heterozygote, and digestible (C homozygote). Genotypes and allelic frequencies for this polymorphism in both groups were compared. We observed a higher but non-significant percentage of T homozygote in the endometriosis women compared with the non-endometriosis women. Proportions of T homozygote/heterozygote/C homozygote for CYP17 in both groups were: (1) 26.1/46.2/27.7% and (2) 17.2/45.3/37.5% (p-value=0.131). T allele was related with higher susceptibility of endometriosis. T and C allele frequencies in both groups were: (1) 49.2/50.8%; (2) 39.8/60.2% (p-value=0.046). Despite the CYP17* T allele appearing to be asscoiatd with a trend of increased risk of endometriosis, CYP17 5′-UTR gene polymorphism might not be a useful marker for prediction of endometriosis susceptibility.

X-ray repair cross-complementing group 4 (XRCC4) promoter -1394( *)T-related genotype, but not XRCC4 codon 247/intron 3 or xeroderma pigmentosum group D codon 312, 751/promoter -114, polymorphisms are correlated with higher susceptibility to myoma.

OBJECTIVE To investigate whether the DNA repair genes, X-ray repair cross-complementing group 4 (XRCC4) and xeroderma pigmentosum group D (XPD), could be useful markers for predicting leiomyoma susceptibility. DESIGN Prospective study. SETTING Departments of gynecology and genetics in medical center. PATIENT(S) Women were divided into leiomyoma (n = 120) and nonleiomyoma groups (n = 112). INTERVENTION(S) XRCC4 (codon 247, promoter -1394, intron 3) and XPD (codon 312, codon 751, promoter -114) polymorphisms were genotyped by polymerase chain reaction with restriction enzyme digestions. MAIN OUTCOME MEASURE(S) Genotypes and allelic frequencies in both groups were compared. RESULT(S) XRCC4 promoter -1394( *)T-related genotype/alleles were associated with higher susceptibility of leiomyoma. Proportions of XRCC4 promoter -1394( *)T homozygote/heterozygote/G homozygote and T/G alleles were [1] 91.7%/6.7%/1.7% and 95%/5% and [2] 79.4%/17.9%/2.7% and 88.4%/11.6%, respectively. Five other single nucleotide polymorphisms were not correlated with leiomyoma susceptibilities. Proportions of XRCC4 codon 247( *)CC/CA/AA and XRCC4 intron 3( *)II/ID/DD were [1] 95%/5%/0% and 72.5%/23.3%/4.2% and [2] 97.3%/2.7%/0 and 70.5%/24.1%/5.4%. Proportions of XPD codon 312( *)GG/GA/AA, XPD codon 751( *)TT/TG/GG, and XPD promoter -114( *)GG/GC/CC were [1] 65%/22.5%/12.5%, 92.5%/6.7%/0.8%, and 22.5%/46.7%/30.8%; and [2] 64.3%/22.3%/13.4%, 92%/7.1%/0.9%, and 23.2%/46.4%/30.4%. CONCLUSION(S) XRCC4 promoter -1394( *)T-related genotype/alleles are associated with higher susceptibility of leiomyoma, whereas XRCC4 codon 247, XRCC4 intron 3, XPD codon 312, XPD codon 751, and XPD promoter -114 polymorphisms are not correlated with its development.

T allele for VEGF-460 Gene Polymorphism at 5′-Untranslated Region is Associated with Higher Susceptibility of Leiomyoma

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.

In vivo gene transfer of leukemia inhibitory factor (LIF) into mouse endometrium

AbstractPurpose: Leukemia inhibitory factor (LIF) is important for embryogenesis and implantation. We aimed to transfect LIF gene into the mouse endometrium. Materials and Methods: Expression plasmids carried LIF and luciferase genes for transfer. After superovulation, 100 ICR mice were mated with vasectomized mice. Then LIF–liposome (Group 1) and luciferase–liposome complexes (Group 2) were injected into their uterine lumen (Day 0). Endometrial LIF and luciferase expressions were detected by reverse transcription-polymerase chain reaction on Days 0–4 post gene transfer. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an internal control to normalize the gene transfection. Results: LIF mRNA and luciferase activities reached the peak expression on Day 3. In Group 1, the ratios of LIF/GADPH on Days 1–4 were 0.414, 1.096, 1.162, and 0.782. In Group 2, LIF/GADPH on Days 1–4 were 0.24, 0.22, 0.35, and 0.32. Conclusions: Mouse endometrium could be effectively transfected with liposome–DNA mixtures. Endometrial LIF transfer via liposome may be effective in human.