A new TEX11 mutation causes azoospermia and testicular meiotic arrest.

There are many unknown genetic factors that lead to infertility in nonobstructive azoospermia men. Here, we performed whole-exome sequencing in blood samples obtained from 40 azoospermia patients with meiotic arrest and found a novel c.151_154del (p.D51fs) frame-shift mutation in exon 3 of the testis expressed 11 (TEX11) gene in one patient. Sanger sequencing analysis of the patient and 288 fertile men was performed to validate the mutation. Immunohistochemical analysis showed TEX11 expression in late-pachytene spermatocytes and in round spermatids in fertile human testes. In contrast, testes of the patient with TEX11 mutation underwent meiotic arrest and lacked TEX11 expression. Western blotting of human embryonic kidney (HEK293) cells transfected with a vector for the p.D51fs TEX11 variant detected no TEX11 expression. In conclusion, we identified a novel frame-shift mutation in the TEX11 gene in an azoospermia patient, emphasizing that this gene should be included in genetic screening panels for the clinical evaluation of azoospermia patients.

Mutational analysis of the GATA4 gene in Chinese men with nonobstructive azoospermia.

As a crucial transcription factor for spermatogenesis, GATA-binding protein 4 (GATA4) plays important roles in the functioning of Sertoli and Leydig cells. Conditional knockout of GATA4 in mice results in age-dependent testicular atrophy and loss of fertility. However, whether GATA4 is associated with human azoospermia has not been reported. Herein, we analyzed the GATA4 gene by direct sequencing of samples obtained from 184 Chinese men with idiopathic nonobstructive azoospermia (NOA). We identified a missense mutation (c.191G>A, p.G64E), nine single-nucleotide polymorphisms (SNPs), and one rare variant (c.*84C>T) in the 3´ untranslated region (UTR). Functional studies demonstrated that the p.G64E mutation did not affect transactivation ability of GATA4 for spermatogenesis-related genes (claudin-11 and steroidogenic acute regulatory protein, Star), and the 3´ UTR rare variant c.*84C>T did not generate microRNA-binding sites to repress GATA4 expression. To our knowledge, this is the first report to investigate the association between GATA4 and azoospermia; our results indicate that mutations in GATA4 may not be pathogenic for NOA in Chinese men.

Predictive significance of serum inhibin B on testicular haploid gamete retrieval outcomes in nonobstructive azoospermic men.

The purpose of this study was to determine the diagnostic accuracy of serum inhibin B (INHB) as a predictor of the retrieval outcome of testicular haploid gametes (spermatids and testicular spermatozoa) in nonobstructive azoospermic men. Serum hormone levels, testicular volume, and histological evaluation were performed in 403 Chinese nonobstructive azoospermic men. Testicular haploid gamete was successfully retrieved in 213 of 403 patients (52.85%). The haploid gamete group always had higher INHB levels than the non-haploid gamete group. According to the receiver operating characteristic (ROC) curve analysis, INHB was a good predictor of testicular haploid gamete retrieval outcome in all patients (sensitivity: 77.93% and specificity: 91.58%) and patients with normal follicle-stimulating hormone (FSH; sensitivity: 88.52% and specificity: 70.83%). The area under the ROC curve (AUC) of INHB was similar to that of FSH in all patients or patients with normal FSH. In patients with elevated FSH, INHB was superior to FSH in predicting the presence of haploid gamete (AUC: 0.73 vs 0.55, P < 0.05), with a sensitivity of 60.00% and a specificity of 80.28%. It concluded that serum INHB as an effective marker for spermatogenesis was a significant predictor of testicular haploid gamete retrieval outcomes in nonobstructive azoospermic men. Especially, INHB is superior to FSH in predicting the presence of haploid gamete in the patients with elevated FSH.

Outcomes of Preimplantation Genetic Diagnosis Cycles by Fluorescent In situ Hybridization of Infertile Males with Nonmosaic 47,XYY Syndrome.

BACKGROUND: The 47,XYY syndrome could result in fertility problems. However, seldom studies reported comprehensive researches on the embryonic development and pregnancy outcomes of these patients. This study aimed to evaluate the clinical outcomes of nonmosaic 47,XYY patients performed with fluorescent in situ hybridization (FISH) and preimplantation genetic diagnosis (PGD) treatment. METHODS: This was a retrospective study. Between January 2012 and May 2017, 51 infertile males with nonmosaic 47,XYY syndrome underwent FISH-PGD were included in the study. According to sex chromosomal FISH results, embryos were classified as normal signal, no nuclei fixed, no signal in fixed nuclei, suspensive signal, and abnormal signal groups, respectively. The incidence of each group, the fixation rate, and hybridization rate were calculated. Embryonic development and pregnancy outcomes were also analyzed. The measurement data were analyzed with Student's t-test. The comparison of categorical data was analyzed with the Chi-square test and Fisher's exact test when expected cell count was <5. RESULTS: The 53 PGD cycles with 433 embryos were analyzed. The fixation rate was 89.6%, while the hybridization rate was 96.4%. There were 283 embryos with two sex chromosomal signals with clear diagnosis (65.4%). The numbers of no nuclei fixed, no signal in fixed nuclei, suspensive signal, and abnormal signal groups were 45 (10.4%), 14 (3.2%), 24 (5.5%), and 67 (15.5%), respectively. Embryos with abnormal signals were abandoned. The number of good-quality embryos was 210 (57.4%), including implanted embryos on day 4/day 5 and cryopreserved. The rates of good-quality embryos in the no nuclei fixed (22.2%), no signal in fixed nuclei (28.6%), and suspensive signal groups (33.3%) were comparable (P > 0.05), and were significantly lower than the normal signal group (66.4%, P < 0.001). The clinical pregnancy rates of fresh and frozen embryos transferred cycles were 70.6% and 85.7%, respectively. CONCLUSIONS: Among embryos with a clear diagnosis of sex chromosome, about one-fifth showed abnormal signals. Embryos with two sex chromosomal signals are more likely to develop into good-quality ones. The application of the PGD by FISH may help to improve the clinical outcome s.

Decline of semen quality among Chinese sperm bank donors within 7 years (2008-2014).

Semen from 5210 sperm bank donors was analyzed and trends in semen quality were evaluated at Shandong Human Sperm Bank between 2008 and 2014. After 2-7 days of abstinence, semen samples were collected. Measurements of semen volume, sperm concentration, sperm forward motility, and total sperm count were performed. There were significant declining trends in semen volume, sperm concentration, sperm forward motility, and total sperm count. Our results indicate that the quality of semen in this cohort of sperm donors had decreased during the study period.

Therapeutic effects of fucoidan in 6-hydroxydopamine-lesioned rat model of Parkinson's disease: Role of NADPH oxidase-1.

AIMS: To explore the effect of fucoidan treatment on oxidative stress-mediated dopaminergic neuronal damage and its potential mechanisms. METHODS: The effect of fucoidan was investigated in a 6-hydroxydopamine (6-OHDA) rat model of PD, an animal model considered appropriate for preclinical studies of PD therapy. The effects of fucoidan treatment on animal behavior and the survival ratio of dopaminergic neurons were investigated. We further observed the effect of fucoidan on microglia and the NADPH oxidases-1 (Nox1), a family of enzymes generating reactive oxygen species (ROS). RESULTS: We found that chronic fucoidan administration mitigated the motor dysfunction induced by 6-OHDA. Similarly, fucoidan reduced the loss of DA neurons in the SNc and DA fibers in the striatum in 6-OHDA-lesioned rats. Moreover, we found that fucoidan inhibited the 6-OHDA-stimulating expression of Nox1 in both tyrosine hydroxylase (TH)-positive neurons and non-TH-positive neurons, prevented Nox1-sensitive oxidative stress and cell damage in SNc neurons. Fucoidan also effectively inhibited nigral microglial activation. CONCLUSION: These results support the beneficial effect of fucoidan in 6-OHDA-lesioned rat model of PD. Fucoidan may suppress the Nox1-triggered oxidative stress in the SNc to protect DA neurons from 6-OHDA-induced toxicity and achieve its beneficial effect.

Tenuigenin attenuates α-synuclein-induced cytotoxicity by down-regulating polo-like kinase 3.

BACKGROUND AND AIMS: Tenuigenin (Ten) is a Chinese herbal extract with antioxidative and antiinflammatory effects on toxin-induced cell models of Parkinson's disease (PD); however, its effects on α-synuclein toxicity-based PD models remain unknown. α-synuclein hyperphosphorylation is a key event in PD pathogenesis and potential target of therapeutic interventions. We tested whether Ten alleviates α-synuclein-induced cytotoxicity via reducing kinases that phosphorylate α-synuclein. METHODS: SH-SY5Y cells transiently transfected with wild-type or A53T mutant α-synuclein were used to evaluate the effect of Ten on the levels of α-synuclein phosphorylation-related kinases. Cells treated with 10 µM Ten for 24 h were measured for viability (proliferation and apoptosis assays) and cellular proteins harvested and fractioned. The levels of total and phosphorylated α-synuclein and five associated kinases (polo-like kinase [PLK] 1-3, casein kinase [CK] 1-2) were evaluated by Western blotting. RESULTS: Overexpression of either wild-type or A53T mutant α-synuclein decreased cell viability and increased α-synuclein phosphorylation. Ten treatment-protected cells from this α-synuclein-induced toxicity and dramatically reduced α-synuclein phosphorylation and PLK3 (but not other kinase) levels. CONCLUSION: In α-synuclein cell model of PD, Ten is effective in attenuating α-synuclein-induced toxicity and α-synuclein phosphorylation probably via targeting PLK3, suggesting it could be an efficient therapeutic drug to treat α-synuclein-related neurodegeneration.

Laparoscopic surgery for inflammatory bowel disease--the experience in China.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) has risen rapidly in China over the last 15 years. Increasing numbers of people with IBD require surgery during their lifetime, but few reports of IBD in Eastern populations have been described to date. The aim of this study was to assess the short-term effects of the laparoscopic surgery for IBD in Chinese patients. MATERIALS AND METHODS: From February 2010 to March 2012, 35 patients with IBD underwent laparoscopic operations and the clinical data obtained for these patients were reviewed. RESULTS: Patients with Crohn's disease (CD) (N = 21) and ulcerative colitis (UC) (N = 14) underwent laparoscopic surgery. In the CD group, the mean age was 37.4 years. Two patients (9.5%) required conversion to an open procedure. The median length of postoperative hospitalization was 9 (7-40) days. Overall morbidity was 26.3% and no patients required re-operation. In the UC group, the mean age was 55.2 years. The conversion rate was 14.3% (2/14). The median time to regular diet was 4 (3-10) days and the median length of postoperative hospitalization was 8 (7-25) days. Four patients developed postoperative complications and one patient developed ileostomy retraction requiring urgent operative intervention to rebuild the stoma. CONCLUSIONS: Laparoscopic surgery in patients with IBD can be accomplished safely and with reasonable operative times, conversion rates and morbidity rates. The main advantages of the laparoscopic approach are rapid recovery, improved cosmesis, less postoperative pain, and patient satisfaction.

Ileal pouch anal anastomosis with modified double-stapled mucosectomy--the experience in China.

AIM: To investigate the feasibility and long-term functional outcome of ileal pouch-anal anastomosis with modified double-stapled mucosectomy. METHODS: From January 2002 to March 2011, fourty-five patients underwent ileal pouch anal anastomosis with modified double-stapled mucosectomy technique and the clinical data obtained for these patients were reviewed. RESULTS: Patients with ulcerative colitis (n = 29) and familial adenomatous polyposis (n = 16) underwent ileal pouch-anal anastomosis with modified double-stapled mucosectomy. Twenty-eight patients underwent one-stage restorative proctocolectomy, ileal pouch anal anastomosis, protective ileostomy and the ileostomy was closed 4-12 mo postoperatively. Two-stage procedures were performed in seventeen urgent patients, proctectomy and ileal pouch anal anastomosis were completed after previous colectomy with ileostomy. Morbidity within the first 30 d of surgery occurred in 10 (22.2%) patients, all of them could be treated conservatively. During the median follow-up of 65 mo, mild to moderate anastomotic narrowing was occurred in 4 patients, one patient developed persistent anastomotic stricture and need surgical intervention. Thirty-five percent of patients developed at least 1 episode of pouchitis. There was no incontinence in our patients, the median functional Oresland score was 6, 3 and 2 after 1 year, 2.5 years and 5 years respectively. Nearly half patients (44.4%) reported "moderate functioning", 37.7% reported "good functioning", whereas in 17.7% of patients "poor functioning" was observed after 1 year. Five years later, 79.2% of patients with good function, 16.7% with moderate function, only 4.2% of patients with poor function. CONCLUSION: The results of ileal pouch anal anastomosis with modified double-stapled mucosectomy technique are promising, with a low complication rate and good long-term functional results.

Treatment of preoperatively diagnosed colorectal adenomas by transanal endoscopic microsurgery: the experience in China.

INTRODUCTION: Colorectal adenoma is a recognized precancerous lesion that has the potential for malignant transformation. Surgical resection of colorectal adenomas is required for exact diagnosis and treatment. The aim of this study is to assess the safety and therapeutic effect of transanal endoscopic microsurgery for preoperatively diagnosed colorectal adenomas. METHODS: From September 2006 to February 2011, 45 patients with preoperatively diagnosed colon and rectal adenomas underwent transanal endoscopic microsurgery. The clinical data of these patients were reviewed. RESULTS: The mean tumor diameter was 2.2 cm, mean operative time was 65 min, and the mean estimated blood loss was less than 10 mL. There was no conversion to transabdominal procedure. The mean tumor distance from the anal verge was 8.2 cm. Four patients had perforation into the peritoneal cavity during full-thickness resection; these were repaired by continuous suturing, and there was no postoperative leakage after 1 week of fasting. The surgical margins of specimens were negative in 44 patients. Complications included rectal bleeding in one patient, acute urinary retention in one patient and pulmonary infection in one patient. The mean postoperative hospital stay was 4.5 days. Only one patient experienced incontinence of hard stool 6 months after surgery. The patients were followed up for a median period of 42 months, with four cases of tumor recurrence observed. CONCLUSION: Transanal endoscopic microsurgery is a safe and effective technique for excising large adenomas in the mid and upper rectum and in the lower sigmoid colon. It is also an oncologically preferred method for T1 focal carcinomas that develop from villous adenomas.

Long-term results of intersphincteric resection for low rectal cancer.

BACKGROUND: The aim of this study is to investigate the long-term therapeutic outcome of intersphincteric resection (ISR) as the treatment of ultra-low rectal cancer. METHODS: During January 2004 and October 2010, ISR was performed in 60 patients with ultra-low rectal cancer and their survival, local recurrence, and functional outcome were evaluated retrospectively. RESULTS: A total of 60 patients with tumors at a median distance of 42 (range 30-50) mm from the anal verge underwent ISR. Three cases developed anastomotic leakage and two cases developed anastomotic stenosis postoperatively. After a median follow-up of 49 (range 18-90) months, local and distant recurrence occurred in six and four patients, respectively. Five-year overall and disease-free survival rates were 90.0% and 83.3%. Among them, the functional results of 53 patients suggested the mean stool frequency were 3.8 ± 1.3 (range 3-10) per 24 hr. According to Kirwan classification, good continence was shown in 73.6% of the patients. CONCLUSION: This preliminary study indicated that ISR might be a candidate technique in treating patients with ultra-low rectal cancer and achieved satisfactory long-term results in functional and oncologic respects.

Total laparoscopic sigmoid and rectal surgery in combination with transanal endoscopic microsurgery: a preliminary evaluation in China.

BACKGROUND: This study was designed to evaluate the feasibility and safety of total laparoscopic sigmoid and rectal surgery without abdominal incision in combination with transanal endoscopic microsurgery (TEM). METHODS: From May 2010 to October 2011, 34 patients with colon and rectal tumors were treated by total laparoscopic surgery without abdominal incision, and the clinical data of these patients were reviewed. RESULTS: All operations could be successfully accomplished without conversion to open surgery. No diverting ileostomy was created. The average operative time was 151.60 (range, 125-185) minutes. The average blood loss was 200.20 (range, 55-450) ml. All resection margins were negative. Six patients developed postoperative anastomotic leakage. There were no reports of other complications in all patients. CONCLUSIONS: This preliminary study indicated that total laparoscopic sigmoid and rectal surgery in combination with TEM was a safe, feasible, and minimally invasive technique. This advanced surgical technique was developed by combining laparoscopy with the concept of natural orifice transluminal endoscopic surgery.

[Total laparoscopic sigmoid and rectal surgery combined with transanal endoscopic microsurgery].

OBJECTIVE: To investigate the feasibility and short-term outcomes of total laparoscopic sigmoid and rectal surgery combined with transanal endoscopic microsurgery(TEM). METHODS: The clinical data of 26 patients with colorectal carcinoma treated by total laparoscopic surgery with TEM between May 2010 and May 2011 in the Shanghai Ruijin Hospital were retrospectively analyzed. RESULTS: All the 26 operations were successfully accomplished laparoscopically. There was no conversion to open procedure. No diverting ileostomy was made. The mean operative time was (151.6±25.9) min. The mean blood loss was (200.2±114.7) ml. The mean time to first flatus was (2.0±0.5) d. The mean tumor size was (3.0±0.7) cm and all resection margins were negative. The mean number of lymph nodes harvested was (12.9±2.2). Six patients developed postoperative anastomotic leakage, all of who had tumors in the lower rectum. There were no ureteral injury, intestinal obstruction, or pulmonary infection. CONCLUSIONS: Total laparoscopic sigmoid and rectal surgery combined with TEM is a safe and feasible minimally invasive surgery. It is an improvement by combining laparoscopic skills with the concept of natural orifice transluminal endoscopic surgery.

[Analysis of 32 patients with rectal adenoma undergoing transanal endoscopic microsurgery].

OBJECTIVE: To evaluate the safety and outcomes after transanal endoscopic microsurgery (TEM)for rectal adenoma. METHODS: Data of 32 patients undergoing TEM for rectal adenoma between September 2006 and February 2010 in the Ruijin Hospital were reviewed. RESULTS: The adenoma diameter ranged from 0.6 to 10.0(2.3±1.2) cm. The mean operative time was 70(range,20-180) min. The estimated blood loss was less than 10 ml. There were no conversions to transabdominal procedure. Twenty-two(68.8%) patients underwent suturing of the wound, of whom 14 had full-thickness resection. Two patients had perforation into peritoneal cavity during full-thickness resection, which were repaired by continuous suturing and no postoperative leak occurred. R0 resection was achieved in 31(96.9%) patients. Postoperative pathology showed 12 simple adenomas, 10 adenomas with low grade intraepithelial neoplasia, 5 adenomas with high grade intraepithelial neoplasia, and 5 T1 focal carcinomas. Complications included rectal bleeding in 1 patient, acute urinary retention in 1 patient, and pulmonary infection in 1 patient. The postoperative stay was 4.5(3-8) days. The patients were followed-up for a period of 23 months(range, 2-43 months). There were 2 tumors recurred. CONCLUSION: TEM is a safe and effective minimally invasive surgical technique for large rectal adenomas.

Gene-gene interaction between COMT and MAOA potentially predicts the intelligence of attention-deficit hyperactivity disorder boys in China.

The catechol-O-methyltransferase (COMT) gene contains a functional polymorphism (Val158Met) affecting the activity of the enzyme, and the monoamine oxidase A (MAOA) gene contains a VNTR polymorphism (MAOA-uVNTR) that affects the transcription of the gene. COMT and MAOA each contribute to the enzymatic degradation of dopamine and noradrenaline. Prefrontal cortical (PFC) function, which plays an important role in individual cognitive abilities, including intelligence, is modulated by dopamine. Since our previous association studies between attention deficit hyperactivity disorder (ADHD) and these two functional polymorphisms consistently showed the low activity alleles were preferentially transmitted to inattentive ADHD boys, the goal of the present study was to test the hypothesis that the interaction between COMT Val158Met and MAOA-uVNTR may affect the intelligence in a clinical sample of Chinese male ADHD subjects (n = 264). We found that the COMT x MAOA interaction significantly predicted full scale (FSIQ) and performance (PIQ) IQ scores (P = 0.039, 0.011); the MAOA-uVNTR significantly predicted FSIQ, PIQ and verbal IQ (VIQ) (P = 0.009, 0.019, 0.038); COMT Val158Met independently had no effect on any of the IQ scores. Only the COMT x MAOA interaction for PIQ remained significant after a Bonferroni correction. Among all combined genotypes, the valval-3R genotype predicted higher intelligence, (average 106.7 +/- 1.6, 95% C.I. 103.7-109.8 for FSIQ), and the valval-4R predicted lower intelligence (average 98.0 +/- 2.3, 95% C.I. 93.5-102.6 for FSIQ). These results suggest that there is an inverted U-shaped relationship between intelligence and dopaminergic activity in our sample. Our finding that gene-gene interaction between COMT and MAOA predicts the intelligence of ADHD boys in China is intriguing but requires replication in other samples.

[Use of L-carnitine before percutaneous epididymal sperm aspiration-intracytoplasmic sperm injection for obstructive azoospermia].

OBJECTIVE: To explore the use of L-carnitine before percutaneous epididymal sperm aspiration-intracytoplasmic sperm injection (PESA-ICSI) in the treatment of obstructive azoospermia. METHODS: Seventy-nine cases of obstructive azoospermia treated in our center from Sep 2008 to Aug 2009 were divided into an L-carnitine (n = 43) and a control group (n = 36), the former given oral L-carnitine at 1 g bid for 3 months before PESA-ICSI, while the latter left untreated. Comparisons were made between the two groups in the number of retrieved oocytes and fertilized oocytes as well as the number and rate of good embryos. RESULTS: There were no significant differences between the two groups in the number of retrieved oocytes and fertilized oocytes. But the number and rate of good embryos were significantly higher in the L-carnitine than in the control group (P < 0.05). CONCLUSION: Three-month oral medication of L-carnitine before PESA-ICSI can raise the number and rate of good embryos in obstructive azoospermia patients and therefore benefit the therapeutic outcome.

[Value of ligating the middle colic artery from the root in radical surgical treatment of right hemicolon cancer].

OBJECTIVE: To compare the long-term outcome of ligating the middle colic artery in radical surgical treatment of right hemicolon cancer. METHODS: The operation safety, complications and short-term outcome between two groups of patients undergone either ligating the middle colic artery from its root (A group) or ligating the middle colic artery from its right branch (B group) in right hemicolectomy for colon cancer. RESULTS: Between January 1981 and December 2004, 308 patients underwent radical right hemicolectomy in which 103 patients were treated by ligating the middle colic artery from its roots(Jan. 1996 to Dec. 2004, A group), and 205 patients via ligating the middle colic artery from the roots of its right branch(Jan. 1981 to Dec. 1995, B group). The complications were compared between the two groups(P>0.05). The mean follow-up time of A and B group were(50.1+/-7.2) months and(49.1+/-7.2) months respectively. Local recurrences of 1-year, 3-year and cumulative survival probability at the 60th month in group A were 1.9%, 13.6% and(78.3+/-3.4)% respectively, which were significantly better than 19.0%, 24.9% and(64.8+/-2.8)% in group B(P<0.05). CONCLUSION: Ligating the middle colic artery from its root in right hemicolectomy can be performed safely and effectively, which is to be highly recommended in curative resection of right colon.

Early apoptotic changes in human spermatozoa and their relationships with conventional semen parameters and sperm DNA fragmentation.

AIM: To investigate whether early apoptotic changes in spermatozoa can be significant markers for sperm quality. METHODS: Two early apoptotic changes in the semen of 56 men were assessed using Annexin V (AN)/propidium iodide (PI) staining for phosphatidylserine externalization and JC-1 staining for mitochondrial membrane potential (MMP). The results were compared with conventional semen parameters and DNA fragmentation identified using the TUNEL assay. RESULTS: The different labeling patterns in the bivariate Annexin V/PI analysis identified four distinctive spermatozoa populations. The percentage of AN(-)/PI(-) spermatozoa positively correlated with conventional semen parameters and MMP, but negatively correlated with TUNEL (+) spermatozoa. As for the AN(-)/PI(+) fraction, we found an opposite result in comparison to AN(-)/PI(-) spermatozoa. The level of early apoptotic AN(+)/PI(+) spermatozoa negatively correlated with MMP and sperm motility. The level of late apoptotic AN+/PI+ spermatozoa negatively correlated with conventional semen parameters and MMP, and positively correlated with TUNEL (+) spermatozoa. MMP positively correlated with conventional semen parameters, but negatively correlated with TUNEL (+) spermatozoa. CONCLUSION: Although early apoptotic AN+/PI(-) spermatozoa only negatively correlates with sperm motility, the differences in proportion of each subpopulation of spermatozoa (especially, the percentage of AN(-)/PI(-) spermatozoa), and decreased MMP might be significant markers for diagnosing male infertility. They possibly bring additional information to predict the outcome of in vitro fertilization.

[Association between serotonin 1D gene polymorphisms and attention deficit hyperactivity disorder comorbid or not comorbid learning disorder].

OBJECTIVE: To investigate the relationship between two HTR1D gene polymorphisms, 1350T>C and 1236A>G polymorphisms, and attention deficit hyperactivity disorder (ADHD) comorbid or not comorbid learning disorder (LD). METHODS: Blood samples were taken from 91 trios with probands of ADHD comorbid LD and 181 trios with probands of ADHD not comorbid LD. DNA was extracted. 1350T>C and 1236A>G were genotyped by restriction fragment length polymorphism analysis. Transmit/disequilibrium test and haplotype analysis were used to test the association between the two polymorphisms of HTR1D gene and ADHD comorbid or not comorbid LD separately. RESULTS: 1236A allele (chi2=5.306, P=0.021) was over transmitted to probands of ADHD without LD. No biased transmissions of any allele and haplotype were found in families with probands of ADHD with LD. CONCLUSION: whether ADHD comorbid LD or not comorbid LD makes difference at the level of HTR1D gene polymorphism of 1236A>G.

[Association between serotonin 2C gene polymorphisms and attention deficit hyperactivity disorder in children with or without comorbidity of disruptive behavior disorder].

OBJECTIVE: Disruptive behavior disorder (DBD) is one of the main comorbidity of attention deficit hyperactivity disorder (ADHD). Previous studies showed significantly different serotonin function between ADHD children with and without the comorbidity of DBD. Therefore, it is needed to compare these two groups in terms of serotonin receptor gene polymorphisms, which may provide further evidence for the previous studies. The current study aimed to investigate the relationship between two serotonin receptor 2C (HTR2C) gene polymorphisms, that are C-759T and G-697C polymorphisms, and ADHD with or without concomitant DBD. METHOD: Blood samples were taken from 237 trios with probands of ADHD with DBD comorbidity and 251 trios with probands of ADHD without comorbidity of DBD. All the subjects were from the ADHD clinic of Peking University Sixth Hospital. DNA was extracted and PCR was performed to amplify the fragments containing both C-759T and G-697C polymorphisms. AciI was used to detect different alleles of the two polymorphisms. Both allele-based and haplotype-based TDT analyses were used to test the association of the two polymorphisms of HTR2C gene and ADHD with or without comorbidity of DBD. RESULTS: The haplotypes -759C (chi(2) = 4.25, P = 0.04), -697G(chi(2) = 3.21, P = 0.07), as well as -759C/-697G were over-transmitted (chi(2) = 4.31, P = 0.04) to the probands of ADHD without DBD. No biased transmission of any allele and haplotype were found in families with probands of ADHD with DBD. CONCLUSION: ADHD with or without the comorbidity DBD was different at the level of HTR2C gene polymorphisms of C-759T and G-697C. HTR2C is related to ADHD without DBD, while not related to ADHD with DBD. The results suggested that the two groups may have different genetic background, at least in HTR2C.