-
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVE: To evaluate the genetic safety of vitrification on the methylation imprints and the development and fertility potential of prepubertal mouse ovaries. DESIGN: Experimental animal study. SETTING: University-based fertility center. ANIMAL(S): Institute of Cancer Research (ICR) 10-day-old female mice, 10-week-old adult female mice, and 12-week-old adult male mice. INTERVENTION(S): Vitrification of juvenile mouse ovaries was performed using ED20 and EG5.5/30 solutions followed by retrieval of fresh and vitrified-warmed germinal vesicle (GV) oocytes for Snrpn differentially methylated regions (DMR) methylation analyses, collection of mature oocytes from superovulated ovarian grafts, in vitro fertility(IVF), and early embryonic development after heterotopic allotransplantation. MAIN OUTCOME MEASURE(S): Analysis of methylation status of Snrpn-DMR, percentage of fertilization, and blastocysts formation. RESULT(S): Methylation status of Snrpn-DMR from vitrified-warmed GV oocytes did not show significant alteration compared with that of controls, although a significant reduction of viable oocytes was observed. Puberty as well as endocrine function was restored, and no significant difference was shown in number of follicles, percentage of mice retaining fertility, and blastocyst formation among three groups. CONCLUSION(S): Our study proved that vitrification of prepubertal mouse ovaries did not alter the methylation profile of Snrpn-DMR and subsequent allotransplantation; IVF could restore the development and fertility potential.
Fertility and sterility 09/2012; · 3.97 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to explore the polycystic ovary syndrome (PCOS) related single nucleotide polymorphisms (SNPs) rs13405728 (in gene LHCGR), rs13429458 (in gene THADA) and rs2479106 (in gene DENND1A) in women with endometrial carcinoma.
We conducted a case-control study comprising 96 Han Chinese women with endometrial carcinoma, and 192 healthy controls. SNPs rs13405728, rs13429458 and rs2479106 were genotyped by polymerase chain reaction (PCR) and direct sequencing. The effects of body mass index (BMI) and age were evaluated using an unconditional logistic regression model adjusted for potential confounders.
The allele frequencies of SNPs rs2479106 and rs13405728 were significantly different (P<0.05) between endometrial carcinoma group and control group, and the difference was especially significant in the subgroup of endometrioid adenocarcinoma. Genotyping analysis showed that allele G in rs2479106 and allele A in rs13405728 could confer risk to endometrioid adenocarcinoma.
Our results suggest that SNPs rs2479106 in gene DENND1A and rs13405728 in gene LHCGR are associated with endometrioid adenocarcinoma.
Gynecologic Oncology 08/2012; 127(2):403-5. · 3.89 Impact Factor
-
Yongyong Shi,
Han Zhao,
Yuhua Shi,
Yunxia Cao,
Dongzi Yang,
Zhiqiang Li,
Bo Zhang,
Xiaoyan Liang,
Tao Li,
Jianhua Chen, [......],
Dongni Zhao,
Chun-e Ren,
Xiuqing Li,
Wei Zhang,
Yiwen Zhang,
Jiangtao Zhang,
Di Wu,
Changming Zhang,
Lin He,
Zi-Jiang Chen
[show abstract]
[hide abstract]
ABSTRACT: Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10(-8): 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS.
Nature Genetics 08/2012; 44(9):1020-5. · 35.53 Impact Factor
-
Han Zhao,
Jianfeng Xu,
Haobo Zhang,
Jielin Sun,
Yingpu Sun,
Zhong Wang,
Jiayin Liu,
Qiang Ding,
Shaoming Lu,
Rong Shi, [......],
Hong Chen,
Guangyu Li,
Junzhao Zhao,
Shuhua Zou,
Hong Jiang,
Cuifang Hao,
Yueran Zhao,
Jinglong Ma,
S Lilly Zheng,
Zi-Jiang Chen
[show abstract]
[hide abstract]
ABSTRACT: A genome-wide association study of Han Chinese subjects was conducted to identify genetic susceptibility loci for nonobstructive azoospermia (NOA). In the discovery stage, 802 azoospermia cases and 1,863 controls were screened for genetic variants in the genome. Promising SNPs were subsequently confirmed in two independent sets of subjects: 818 azoospermia cases and 1,755 controls from northern China, and 606 azoospermia cases and 958 controls from central and southern China. We detected variants at human leukocyte antigen (HLA) regions that were independently associated with NOA (HLA-DRA, rs3129878, p(combine) = 3.70 × 10(-16), odds ratio [OR] = 1.37; C6orf10 and BTNL2, rs498422, p(combine) = 2.43 × 10(-12), OR = 1.42). These findings provide additional insight into the pathogenesis of NOA.
The American Journal of Human Genetics 04/2012; 90(5):900-6. · 10.60 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In recent years, the role of high mobility group box-1 (HMGB1) protein and its receptors in autoimmune diseases has received increasing attention. It has been documented that HMGB1 is associated with disease activity in patients with systemic lupus erythematosus (SLE). This study was undertaken to determine the potential role of receptor for advanced glycation end products (RAGE), one receptor for HMGB1, in the pathogenesis of SLE. Plasma levels of soluble RAGE (sRAGE) from 105 patients with clinical diagnosis of SLE and 43 healthy controls were determined by ELISA. Associations between sRAGE levels and clinical, laboratory characteristics were assessed. The data showed that plasma levels of sRAGE in patients with SLE were significantly lower than those in healthy controls (HC) (P = 0.003). Plasma sRAGE in patients receiving short-period treatment showed an immediate decrease compared with the untreated patients (P = 0.023). In contrast, plasma sRAGE in patients receiving long-period treatment were significantly increased compared to those with short-period treatment (P = 0.000) and comparable with those in HC (P = 0.305). The significant decreased levels of sRAGE in patients with SLE suggest the potential association of RAGE signalling and SLE clinical pathology, whereas, long-period antilupus treatment may counteract the decreased sRAGE levels in patients with SLE.
Scandinavian Journal of Immunology 02/2012; 75(6):614-22. · 2.23 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Premature ovarian failure (POF) is a complex and heterogeneous disorder that is influenced by multiple genetic components. Numerous candidate gene studies designed to identify POF susceptibility loci have been published, but most positive findings have not been confirmed in follow up studies. We sought to determine if sequence variants previously associated with age at natural menopause (AANM) or early menopause (EM) contribute as well to genetic susceptibility to POF.
Our study was performed on 371 unrelated idiopathic women with POF and 800 women controls, all Chinese Han. Thirty six SNPs from previous genome-wide association studies (GWAS) responsible for AANM or EM and 3 additional SNPs in ESR1, and 2 additional SNPs in PTHB1 were tested using the Sequenom MassARRAY iPLEX platform for genotyping.
Three SNPs - rs2278493 in HK3, rs2234693 in ESR1 and rs12611091 in BRSK1 - showed nominally significant association with POF. Thus, a plausible relationship could exist between ESR1, BRSK1, HK3 and POF.
This largest association study undertaken to determine correlation between POF and AANM/EM revealed three significant SNPs (rs2278493, rs2234693, and rs12611091). All are associated with not only AAWM and EM but also POF. Insights into shared genetic susceptibility between POF and AANM/EM will provide novel entry points for unraveling genetic mechanism involved in ovarian reserve and oocyte aging processes.
Orphanet Journal of Rare Diseases 01/2012; 7:5. · 5.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To find the association between recurrent spontaneous abortion (RSA)/early embryo growth arrest and Y chromosome polymorphism.
Peripheral blood samples of the male patients of big Y chromosome, small Y chromosome and other male patients whose partners suffered from unexplained RSA/early embryo growth arrest were collected. PCR and real-time fluorescent quantitative PCR were used to test the deletion and the copy number variation of DYZ1 region in Y chromosome of the patients. A total of 79 big Y chromosome patients (48 of whose partners suffered from RSA or early embryo growth arrest), 7 small Y chromosome patients, 106 other male patients whose partners had suffered from unexplained RSA or early embryo growth arrest, and 100 normal male controls were enrolled.
There was no fraction deletion of DYZ1 detected both in big Y patients and in normal men. Of RSA patients, 1 case showed deletion of 266bp from the gene locus 25-290bp, and 2 cases showed deletion of 773bp from 1347 to 2119bp. Of only 7 small Y chromosome patients, 2 cases showed deletion of 266bp from 25 to 290bp, and 4 cases showed deletion of 773bp from 1347 to 2119bp and 275bp from 3128 to 3420bp. The mean of DYZ1 copies was 3900 in normal control men; the mean in big Y patients was 5571, in RSA patients was 2655, and in small Y patients was 1059. All of the others were significantly different (P<0.01) compared with normal control men, which meant that DYZ1 copy number in normal control men was less than that of big Y chromosome patients, and was more than that of unexplained early RSA patients and small Y patients.
The integrity and copy number variation of DYZ1 are closely related to the Y chromosome length under microscope. The cause of RSA/early embryo growth arrest in some couples may be the increase (big Y patients) or decrease of DYZ1 copy number in the husbands' Y chromosome.
European journal of obstetrics, gynecology, and reproductive biology 08/2011; 159(2):371-4. · 1.97 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Polycystic ovary syndrome (PCOS) and type 2 diabetes (T2D) are two common metabolic disorders in reproductive-aged women, and both are associated with insulin resistance. Evidence has indicated that the growth hormone receptor (GHR) exon 3 polymorphism is associated with T2D and the GHRd3 allele may have the preventive effect on the disease. However, the genetic effect of this polymorphism on PCOS is unknown. The present study thus aims to evaluate the association between the GHR exon 3 polymorphism and PCOS.
A total of 432 patients with PCOS and 441 healthy control subjects were included. All of them were Han Chinese women and well characterized. Genotyping experiments of GHR exon 3 polymorphism were performed with a standard protocol of PCR and gel electrophoresis.
GHRd3 allele frequency in PCOS patients was significantly higher compared to the control subjects (19.1% vs. 14.3%; P=0.007, OR=1.416; 95% CI=1.099-1.825). Further analyses indicated that the GHRd3 allele was associated with increased waist and hip circumstance in healthy women (P=0.016; 0.003), and also with 1-h, 2-h and area under the curve (AUC) plasma glucose levels among PCOS patients (all P<0.05). But, no association of GHR exon 3 polymorphism with insulin resistance in the patients was observed.
The present study provides the first evidence that GHR exon 3 polymorphism is associated with PCOS in Han Chinese women. The GHRd3 allele may contribute to an impact of glucose metabolism but not insulin resistance.
Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 08/2011; 21(5):248-51. · 2.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Estrogen is the main female hormone of women. It has diverse effects on cell growth, differentiation and homeostatic functions. Accumulated evidence has indicated that estrogen may regulate multiple immune functions and the immune status of women. However, there is little report on the effect of estrogen on mature B cell functions. In this study, we observed the effect of 17β-estradiol (E2) on the proliferation, apoptosis, antibody production and differentiation of splenic B cells of mice in vitro. Splenocytes of female BALB/c mice were isolated and cultured with E2. E2 treatments decreased the expression of CD80 molecule on splenic B cells but enhanced the total IgG antibody production of splenocyte, without promoting the differentiation of B cells to plasma cells. E2 protected splenic B cells from the serum-deficiency-induced apoptosis but had no influence on the proliferation of B cells. These results suggest that estrogen may promote the activity of B cells through down-regulating the expression of CD80 molecule on B cells.
Gynecological Endocrinology 08/2011; 27(8):593-6. · 1.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Melatonin receptor 1A (MTNR1A) gene is a regulator of circadian rhythms and reproductive processes. The MTNR1A gene is also a potential candidate gene of polycystic ovary syndrome (PCOS). The aim of the present study was to determine whether or not the MTNR1A gene polymorphism is associated with a predisposition to PCOS.
The single nucleotide polymorphism (SNP) rs2119882 in the MTNR1A gene was detected in 482 patients with PCOS and 522 healthy Chinese Han women. Subsequently, the association of MTNR1A gene variants with plasma glucose, insulin levels during oral glucose tolerance tests (OGTTs) and hormone levels was investigated.
The frequencies of genotypes and allelotypes of SNP rs2119882 differed significantly between PCOS cases and healthy controls (p < 0.001 and p = 0.002, respectively). SNP rs2119882 was associated with higher fasting plasma glucose concentrations (p = 0.021) and OGTT-induced insulin release at 0, 30, 60, and 120 min (all p < 0.05) in PCOS cases, as well as an increased homeostasis model assessment for insulin resistance (p = 0.005).
SNP rs2119882 is associated with PCOS.
Gynecologic and Obstetric Investigation 04/2011; 72(2):130-4. · 1.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Polycystic ovary syndrome (PCOS) is a complex disease having both genetic and environmental components. Candidate genes with insulin metabolism have been hypothesized to be involved in the etiology of this syndrome. In the present study, we investigated the genetic association between polymorphisms in the insulin receptor (INSR) gene and PCOS.
A total of 260 family trios were recruited and performed a family-based analysis to assess linkage and association between four single nucleotide polymorphisms (SNPs) (rs1799817, rs2059807, rs8108622 and rs10500204) of INSR gene and PCOS.
Using the transmission disequilibrium test (TDT), we failed to find that rs1799817 (p = 0.486), rs2059807 (p = 0.195), rs8108622 (p = 0.866) and rs10500204 (p = 1.0) were significantly overtransmitted to PCOS offspring from their parents.
No significant evidence of association or linkage was found in the four tested markers, indicating that our family samples did not support susceptibility of the INSR gene to PCOS.
Reproductive Biology and Endocrinology 01/2011; 9:76. · 2.05 Impact Factor
-
Zi-Jiang Chen,
Han Zhao,
Lin He,
Yuhua Shi,
Yingying Qin,
Yongyong Shi,
Zhiqiang Li, Li You,
Junli Zhao,
Jiayin Liu, [......],
Cuifang Hao,
Chun-E Ren,
Yajie Zhang,
Shiling Chen,
Wei Zhang,
Aijun Yang,
Junhao Yan,
Yuan Li,
Jinlong Ma,
Yueran Zhao
[show abstract]
[hide abstract]
ABSTRACT: Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rs13405728; combined P-value by meta-analysis P(meta) = 7.55 × 10⁻²¹, odds ratio (OR) 0.71); 2p21 (rs13429458, P(meta) = 1.73 × 10⁻²³, OR 0.67); and 9q33.3 (rs2479106, P(meta) = 8.12 × 10⁻¹⁹, OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended.
Nature Genetics 01/2011; 43(1):55-9. · 35.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Accumulating evidences indicate that killer cell immunoglobulin-like receptors (KIRs) and their corresponding specific HLA-C ligands contribute to the pathogenesis of multiple autoimmune diseases via the modulation of natural killer (NK) cell and T cell functions. The present study was performed to investigate whether the polymorphism of KIR genes and HLA ligands associates with the susceptibility of ankylosing spondylitis (AS). Previous studies have demonstrated a strong association between HLA-B27 gene and the pathogenesis of AS. In this study, 115 unrelated HLA-B27-positive AS patients and 119 HLA-B27-positive healthy controls were recruited. Polymerase chain reaction using sequence-specific primers was used to determine the genotypes of KIR genes and HLA-C alleles. The results showed that the frequencies of KIR2DL1 and KIR2DL5 were significantly higher in the AS patient group than those in the control group (p = 0.012 and p = 0.009, respectively). Meanwhile, individuals with AS showed an increased frequency of HLA-Cw*08 (p = 0.001, p (c) = 0.008) compared with that in controls. Our findings indicate that with the genetic background of HLA-B27, variation at the KIRs and their corresponding specific HLA-C ligands may influence the ability of NK cells and T cells to recognize and lyse targets in immune responses, which thereby contributes to pathogenesis of AS.
Journal of Clinical Immunology 11/2010; 30(6):840-4. · 3.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of the present study was to determine whether or not the 'melatonin receptor (MTNR1B)' gene polymorphisms are associated with a predisposition for polycystic ovary syndrome (PCOS). The single-nucleotide polymorphisms (SNPs), rs10830963 and rs10830962, in the MTNR1B gene were detected in 526 patients with PCOS and 547 healthy Chinese Han women. The association between MTNR1B gene variants and plasma glucose and insulin levels during the oral glucose tolerance test (OGTT) and hormone levels was investigated. The frequencies of three genotypes and two allelotypes of the SNP, rs10830963, differed significantly between women with PCOS and healthy controls (P < 0.001 and P < 0.001, respectively). The SNP, rs10830963, was significantly associated with higher fasting plasma glucose concentrations (P < 0.001) and increased the area under the curve of plasma glucose levels during the OGTT (P < 0.001), as well as increased homeostasis model assessment of insulin resistance (HOMA-IR; P = 0.027). No significant differences were observed in the genotypes and allele distributions of rs10830962 polymorphisms between the PCOS and the control groups (P = 0.311 and P = 0.178, respectively). There was no significant difference in the clinical and the metabolic characteristics in women with PCOS with different genotypes in the SNP, rs10830962 (all P > 0.005). The present study suggest that the SNP, rs10830963, in the MTNR1B gene is not only associated with susceptibility to PCOS, but also contributes to the PCOS phenotype.
Molecular Human Reproduction 10/2010; 17(3):193-8. · 3.85 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: An association of polymorphism -1154G/A (rs1570360) in vascular endothelial growth factor (VEGF) gene with idiopathic recurrent spontaneous abortion (RSA) has been found in Caucasians. The aim of this study was to examine the association of VEGF -1154 with RSA in a well-defined group of Chinese Han patients.
The VEGF -1154G/A genotype was detected by real-time PCR with TaqMan probes. The products were also subjected to gene sequence analysis to validate the PCR results.
The allele frequencies of VEGF -1154G/A showed no significant difference between RSA patients and the normal controls (P = 0.183). The frequencies of VEGF -1154G/A genotypes were not significantly different between RSA patients and the normal controls (P = 0.228).
Our study revealed that VEGF -1154G/A polymorphism was not associated with the susceptibility to RSA in Chinese Han women.
American Journal Of Reproductive Immunology 10/2010; 65(5):521-5. · 2.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate characteristics of glucose metabolism of non-obese and obese women with polycystic ovary syndrome (PCOS).
From May 2006 to April 2009, 1928 PCOS patients treated in Reproductive Medicine Center of Shandong Provincial Hospital Affiliated to Shandong University were enrolled in this study, which were divided into 901 cases [body mass index (BMI) ≥ 25 kg/m²] in obese group and 1027 cases in non-obese (BMI < 25 kg/m(2)) group. The prevalence of type 2 diabetes mellitus (T2DM), oral glucose tolerance test, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) were compared between the two groups.
(1) Blood glucose levels: at the time of fasting, 30, 60, 120 and 180 minutes, the levels of glucose were (5.3 ± 1.1), (9.0 ± 2.4), (9.3 ± 4.4), (7.5 ± 2.8), (5.3 ± 1.8) mmol/L in obese group and (5.0 ± 0.8), (8.4 ± 3.5), (8.0 ± 4.2), (6.5 ± 3.2), (4.9 ± 1.6) mmol/L in non-obese group, which all showed statistical difference at every time point (P < 0.01). (2)The level of insulin: at the time of fasting, 30, 60, 120 min, the level of insulin were (13 ± 7), (81 ± 51), (102 ± 65), (83 ± 63) mU/L in obese group and (8 ± 5), (57 ± 35), (62 ± 44), (46 ± 39) mU/L in non-obese group, which all showed statistical difference at every time point (P < 0.01). However, at time point of 180 minutes, the level of insulin did not exhibit significantly difference between obese and non-obese group (P > 0.05). (3) The prevalence of abnormal glucose metabolism: the rate of IFG was 4.98% (96/1928). The rate of abnormal glucose tolerance was 23.08% (445/1928). The rate of IGT were 13.05% (134/1027) in non-obese group and 24.20% (218/901) in obese group, which also showed remarkable difference (P < 0.01). The rate of T2DM were 2.53% (26/1027) in non-obese group and 7.44% (67/901) in obese group, which reached significant difference (P < 0.01).
Abnormal glucose metabolism was observed more frequently in overweight or obese PCOS women.
Zhonghua fu chan ke za zhi 08/2010; 45(8):575-7.
-
[show abstract]
[hide abstract]
ABSTRACT: To confirm the clinical diagnosis of complete androgen insensitivity syndrome (CAIS) by molecular genetic testing in a large family.
PCR was performed to amplify the coding region of androgen gene, followed by direct sequencing in the patients with CAIS and relatives in this family.
A missense mutation Arg773His was identified in the patients (homozygous) and carriers (heterozygous).
Mutation Arg773His in the AR gene leads to CAIS in this family. Molecular genetic testing of CAIS facilitates not only prenatal genetic diagnosis but also preimplantation genetic diagnosis and offers genetic counseling for future pregnancies to abandon the transmission of the mutated X chromosome to the coming generation.
Zhonghua fu chan ke za zhi 12/2008; 43(11):828-30.
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the association of polymorphism of codon 121 in the ecto-nucleotide pyrophophastase/phosphodiesterase 1 (E-NPP1/PC-1) gene in Chinese women with polycystic ovary syndrome (PCOS).
A total of 51 PCOS patients and 61 healthy women from the Chinese Han population from the Center Reproductive Medicine of Provincial Hospital affiliated to Shandong University from June 2005 to July 2006 were recruited for the determination of the polymorphism of the E-NPP1/PC-1 gene. Genomic DNA was extracted from peripheral blood monocytes of patients and controls, and genotyping of the gene was performed by using polymerase chain reaction, which was followed by sequencing.
The frequency of the 121Q allele was 13 and 18%, respectively, in PCOS patients and healthy women, while the frequency of the 121K allele was 87 and 82% in the 2 groups. There is no significant difference in the E-NPP1/PC-1 polymorphism between PCOS patients and healthy controls among Chinese Han women.
Ecto-nucleotide pyrophophastase/phosphodiesterase 1 polymorphism has no association with PCOS. Further studies are still needed to elucidate whether or not the E-NPP1/PC-1 gene has a functional role in PCOS.
Saudi medical journal 09/2008; 29(8):1119-23. · 0.52 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: An emerging body of evidence is accumulating to suggest that killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands contribute to the pathogenesis of diverse kinds of autoimmune diseases. However, the functional effects of their polymorphism remain largely unknown to date. Thus, the present study was undertaken to determine the association of the polymorphisms KIRs gene and HLA-C alleles with the susceptibility to ankylosing spondylitis (AS) by means of polymerase chain reaction/sequence-specific primers for genotyping KIRs from genomic DNA of 119 patients with AS together with 128 healthy donors as a control group.
We found that the frequencies of KIR3DS1 and KIR2DL5 were statistically significantly higher in the patient group than those in the control group (P = 0.016 and P = 0.003, respectively). Meanwhile, the percentage of patients, who were carrying two or more of the activating KIRs, was higher than that of control group. With respect to HLA-C alleles, individuals with AS showed an increased frequency of HLA-Cw02. If HLA-C was divided into group 1 or group 2 based on whether there was an asparagine or lysine present at position 80 of the alpha-chain, HLA-C group 2 was more common in subjects with AS compared to control subjects. The genotype 2DS1+/HLA-C lys(80)+ was more common in subjects with AS. Moreover, the CD69 expression, a NK activation marker, remarkably increased in patient with AS.
In conclusions, this study suggests that KIR3DS1 may severe as AS susceptive genes to trigger continuous injury of arthrosis. The imbalance of activating and inhibitory KIR as well as HLA-C group 1 and group 2 may be the key factor, which influences the pathogenesis of AS. Moreover, KIR2DS1 might associate with the susceptibility of AS by influencing NK cell activity once group 2 HLA-C ligands are present.
Journal of Clinical Immunology 08/2008; 28(4):343-9. · 3.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To explore the drug treatment for temporary ejaculation failure in couple undergoing assisted reproductive technologies (ART).
Case report.
Andrology unit, center for reproductive medicine. PATIENT (S): Five patients suffering from temporary ejaculation failure during ART.
Assisted reproductive technology. Semen samples were collected by masturbation. The combined use of phosphodiesterase-5 inhibitor (PDE5-I; vardenafil, 10 mg) and selective serotonin reuptake inhibitor (SSRI; sertraline, 50 mg) to treat patients who failed to collect semen on the day of egg retrieval.
Five patients with unexpected ejaculation failure during ART treatments were identified; two patients could not produce spermatozoa 3 h after taking PDE5-I (sildenafil, 50 mg), However, the use of PDE5-I (vardenafil, 10 mg) plus SSRI (sertraline, 50 mg) enabled them to provide spermatozoa successfully. It suggested that the combined protocol could be more efficient for temporary ejaculation failure than sildenafil alone. On the day of the egg retrieval, we directly prescribed vardenafil and sertraline for the other three patients and got sperm samples without difficulty 2 h later.
The results indicate that the combined protocol of vardenafil plus sertraline could resolve the unpredictable ejaculation failure during ART. We presume that it might be helpful for attenuating the patients' stress and anxiety.
Fertility and sterility 05/2008; 91(5):1806-8. · 3.97 Impact Factor
