Causal effects of serum testosterone levels on brain volume: a sex-stratified Mendelian randomization study.

PURPOSE: To assess the causal effects of serum testosterone and sex hormone-binding globulin levels on brain volumetric measurements in women and men. METHODS: We performed a sex-stratified two-sample Mendelian randomization study using the random-effects inverse variance-weighted method as the primary analysis method. Sex-specific genetic instruments were obtained from a study with up to 194,453 men and 230,454 women. For testosterone, variants with dominant effects on both total and bioavailable testosterone but no aggregate effect on sex hormone-binding globulin were used as the main genetic instruments. Sex-specific summary-level data for magnetic resonance imaging brain volumetric measurements were obtained from a study with 11,624 women and 10,514 men. RESULTS: Analyses showed per standard deviation (approximately 3.7 nmol/L) higher testosterone levels in men were suggestively associated with larger gray matter volume (beta = 0.208, 95% confidence interval = 0.067 to 0.349, p = 0.004). The association remained in sensitivity analyses and multivariable analyses. Further analyses showed the effect was mainly act on peripheral cortical gray matter, but not on subcortical gray matter. Testosterone in men was not associated with hippocampal volume. Testosterone in women and sex hormone binding globulin in both sexes had no effect on all outcomes. CONCLUSION: Our findings overall support previous evidence that testosterone might have neuroprotective properties in elderly men. Future larger trials with long duration of intervention are warranted to assess the efficacy of testosterone for elderly men with cognitive impairment, especially in those with hypoandrogenism.

[Concordance between three integrated scores based on prostate biopsy and grade-grouping of radical prostatectomy specimen].

Objective: To analyze three different integrated scoring schemes of prostate biopsy and to compare their concordance with the scoring of radical prostatectomy specimens. Methods: A retrospective analysis of 556 patients with radical prostatectomy performed in Nanjing Drum Tower Hospital, Nanjing, China from 2017 to 2020. In these cases, whole organ sections were performed, the pathological data based on biopsy and radical prostatectomy specimens were summarized, and 3 integrated scores of prostate biopsy were calculated, namely the global score, the highest score and score of the largest volume. Results: Among the 556 patients, 104 cases (18.7%) were classified as WHO/ISUP grade group 1, 227 cases (40.8%) as grade group 2 (3+4=7); 143 cases (25.7%) as grade group 3 (4+3=7); 44 cases (7.9%) as grade group 4 (4+4=8) and 38 cases (6.8%) as grade group 5. Among the three comprehensive scoring methods for prostate cancer biopsy, the consistency of global score was the highest (62.4%). In the correlation analysis, the correlation between the scores of radical specimens and the global scores was highest (R=0.730, P<0.01), while the correlations of the scores based on radical specimens with highest scores and scores of the largest volume based on biopsy were insignificant (R=0.719, P<0.01; R=0.631, P<0.01, respectively). Univariate and multivariate analyses showed tPSA group and the three integrated scores of prostate biopsy were statistically correlated with extraglandular invasion, lymph node metastasis, perineural invasion and biochemical recurrence. Elevated global score was an independent prognostic risk factor for extraglandular invasion and biochemical recurrence in patients; increased serum tPSA was an independent prognostic risk factor for extraglandular invasion; increased hjighest score was an independent risk factor for perineural invasion. Conclusions: In this study, among the three different integrated scores, the overall score is most likely corresponded to the radical specimen grade group, but there is difference in various subgroup analyses. Integrated score of prostate biopsy can reflect grade group of radical prostatectomy specimens, thereby providing more clinical information for assisting in optimal patient management and consultation.

[Expression of GPNMB in renal eosinophilic tumors and its value in differential diagnosis].

Objective: To investigate the expression of glycoprotein non metastatic melanoma protein B (GPNMB) in renal eosinophilic tumors and to compare the value of GPNMB with CK20, CK7 and CD117 in the differential diagnosis of renal eosinophilic tumors. Methods: Traditional renal tumor eosinophil subtypes, including 22 cases of renal clear cell carcinoma eosinophil subtype (e-ccRCC), 19 cases of renal papillary cell carcinoma eosinophil subtype (e-papRCC), 17 cases of renal chromophobe cell carcinoma eosinophil subtype (e-chRCC), 12 cases of renal oncocytoma (RO) and emerging renal tumor types with eosinophil characteristics [3 cases of eosinophilic solid cystic renal cell carcinoma (ESC RCC), 3 cases of renal low-grade eosinophil tumor (LOT), 4 cases of fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) and 5 cases of renal epithelioid angiomyolipoma (E-AML)], were collected at the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2017 to March 2022. The expression of GPNMB, CK20, CK7 and CD117 was detected by immunohistochemistry and statistically analyzed. Results: GPNMB was expressed in all emerging renal tumor types with eosinophil characteristics (ESC RCC, LOT, FH-dRCC) and E-AML, while the expression rates in traditional renal eosinophil subtypes e-papRCC, e-chRCC, e-ccRCC and RO were very low or zero (1/19, 1/17, 0/22 and 0/12, respectively); the expression rate of CK7 in LOT (3/3), e-chRCC (15/17), e-ccRCC (4/22), e-papRCC (2/19), ESC RCC (0/3), RO (4/12), E-AML(1/5), and FH-dRCC (2/4) variedly; the expression of CK20 was different in ESC RCC (3/3), LOT(3/3), e-chRCC(1/17), RO(9/12), e-papRCC(4/19), FH-dRCC(1/4), e-ccRCC(0/22) and E-AML(0/5), and so did that of CD117 in e-ccRCC(2/22), e-papRCC(1/19), e-chRCC(16/17), RO(10/12), ESC RCC(0/3), LOT(1/3), E-AML(2/5) and FH-dRCC(1/4). GPNMB had 100% sensitivity and 97.1% specificity in distinguishing E-AML and emerging renal tumor types (such as ESC RCC, LOT, FH-dRCC) from traditional renal tumor types (such as e-ccRCC, e-papRCC, e-chRCC, RO),respectively. Compared with CK7, CK20 and CD117 antibodies, GPNMB was more effective in the differential diagnosis (P<0.05). Conclusion: As a new renal tumor marker, GPNMB can effectively distinguish E-AML and emerging renal tumor types with eosinophil characteristics such as ESC RCC, LOT, FH-dRCC from traditional renal tumor eosinophil subtypes such as e-ccRCC, e-papRCC, e-chRCC and RO, which is helpful for the differential diagnosis of renal eosinophilic tumors.

[Application of skin phosphorylated synuclein in the diagnosis of dementia with Lewy body].

Patients with dementia with Lewy body(DLB), Alzheimer disease (AD), frontotemporal dementia (FTP), progressive supranuclear palsy (PSP) and healthy controls in the Department of Neurology, the First Affiliated Hospital of Zhengzhou University from August 2019 to March 2021 were recruited, with 3 in each group. Phosphorylated α-synuclein from the skin of DLB patients was detected by skin micro-biopsy and compared with patients with AD, FTP, PSP and health controls. Phosphorylated α-synuclein was found in the skin nerves of the DLB patients, while no α-synuclein were detected in the skin samples of others. Skin phosphorylated α-synuclein may potentially become a diagnostic biomarker of DLB, however further studies are warranted to assess its sensitivity and specificity.

[The correlation between plasma heat shock proteins 90α levels and white matter hyperintensity in patients with cerebral small vessel disease].

Objective: To investigate the relationship between plasma heat shock proteins 90α(Hsp90α) levels and the white matter hyperintensity(WMH) in patients with cerebral small vessel disease(SVD). Methods: Patients admitted to the Department of Neurology, the First Affiliated Hospital of Zhengzhou University from March to August 2021 and diagnosed with WMH by magnetic resonance examination (MRI) were selected as the case group, matched with physical examination patients who visited the Department of Medical Examination during the same period and showed no WMH on MRI and no history of neurological diseases as the control group, and the level of plasma Hsp90α was quantitatively detected by enzyme-linked immunosorbent assay. Mann-Whitney U test was used to compare whether there was a difference in plasma Hsp90α levels between the control group and the case group.Multivariate logistic regression analysis was used to explore the related factors of WMH in patients with SVD. Results: Of the 183 subjects, the control group (n=73) consisted of 28 males and 45 females, aged (54±10) years, while the case group (n=110) consisted of 71 males and 39 females, aged (64±10) years old. Plasma Hsp90α level was higher in the case group than that of the control group [53.33(35.33, 70.09) ng/ml vs 35.02(18.51, 54.95) ng/ml, P<0.001]. After adjusting for confounding factors by multivariate analysis, the results showed that plasma Hsp90α levels greater than 58.34 ng/ml was associated with WMH (P=0.002, OR=5.931, 95%CI:1.955-17.995). Conclusion: Higher level of plasma Hsp90α is associated with WMH in patients with SVD.

[The prevalence of atrial cardiomyopathy in patients with different types of acute ischemic stroke and its relationship with cryptogenic stroke].

Objective: To investigate the prevalence of atrial cardiomyopathy in patients with different types of acute ischemic stroke and its relationship with cryptogenic stroke. Methods: Patients with acute ischemic stroke within 7 days of onset who were admitted to the Department of Neurology of the First Affiliated Hospital of Zhengzhou University from January to September 2019 were prospectively and consecutively enrolled. All included patients were classified according to TOAST classification of ischemic stroke. Chi-square test was used to compare the prevalence of atrial cardiomyopathy among patients with different TOAST classifications. Multivariate logistic regression model was used to analyze the related factors of cryptogenic stroke. Results: A total of 1 098 patients with acute ischemic stroke were enrolled in the study, including 661 males and 437 females, with a median age [M(Q1,Q3)] of 61 (53, 68) years. The prevalence of atrial cardiomyopathy in patients with cryptogenic stroke[53.5% (46/86)] was higher than that in patients with large artery atherosclerosis [38.0%(63/166), P=0.018] and small vessel occlusion [19.4%(37/191), P<0.001], but was lower than that of patients in the cardioembolic group [97.3% (72/74), P<0.001]. Multivariate logistic regression analysis showed that atrial cardiomyopathy was an associated factor for cryptogenic stroke (OR=2.945, 95%CI: 1.766-4.911, P<0.001). Conclusions: Atrial cardiomyopathy is associated with cryptogenic stroke. The prevalence of atrial cardiomyopathy in patients with cryptogenic stroke is higher than that in patients with large artery atherosclerosis and small vessel occlusion, but lower than that in patients with cardiac embolism.

Effects of growth hormone on pregnancy rates of patients with thin endometrium.

PURPOSE: To investigate whether growth hormone (GH) could improve pregnancy rates of patients with thin endometrium by clinical study and laboratory experiments. MATERIALS AND METHODS: Ninety-three patients were randomized to either the GH-received group (40) or the routine exogenous administration of estrogens control group (53) for clinical study. The human endometrial carcinoma cell line RL95-2 was used for testing the role of GH with Western blot and real-time PCR by exposure to various concentrations of GH (0.1 nM,1 nM,10 nM,100 nM). RESULTS: Patients treated with GH had a significantly (P < 0.05) greater endometrium thickness on day 3 (7.87±0.72 vs 6.34±0.86), higher implantation rates (24.4% vs 10.5%) and greater clinical pregnancy rates (42.5% vs 18.9%) compared with the control group. No adverse events were associated with the use of GH. Administration of GH significantly up-regulated the expression of VEGF, ItgB3 and IGF-I expression in RL95-2 cells at both mRNA and protein levels (P < 0.05). AG490, an inhibitor of JAK2, nearly completely inhibited the up-regulative effect of GH through the JAK2-STAT5 pathway, and GH-induced effects could be mediated through autocrine IGF-I together with its hepatic counterpart. IGF-I mRNA was detected in the RL95-2 cells. CONCLUSION: GH may improve pregnancy outcomes of patients with thin endometrium who undergo frozen embryo transfer by acting on human endometrial cells to promote proliferation and vascularization and to up-regulate receptivity-related molecular expression.

Correction to: Effects of growth hormone on pregnancy rates of patients with thin endometrium.

Unfortunately, there are errors that occurred in the name and manufacture of the growth hormone (GH) received by the patients in the GH group on page two, Table 1 and figure 1 on page three.

[Efficacy of nasal CPAP and aerobic exercise of different intensity in patients with obstructive sleep apnea hypopnea syndrome and type 2 diabetes mellitus].

Objective: To explore the therapeutic efficacy of nasal Continuous Positive Airway Pressure (CPAP) and aerobic exercise of different intensity in patients with Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) and Type 2 Diabetes Mellitus (T2DM). Methods: A total of 112 patients with OSAHS and T2DM, including 53 males and 59 females, with a mean age of (66.9±7.8) years old, from the Fourth Rehabilitation Hospital of Shanghai and the Second Affiliated Hospital of Soochow University from January 2017 to December 2018 were enrolled prospectively. There were divided into two groups based on whether received nasal CPAP therapy: 50 cases in nasal CPAP+aerobic exercise group and 62 cases in aerobic exercise group. Subsequently, patients in nasal CPAP+aerobic exercise group were randomly divided into two subgroups: moderate and low intensity aerobic exercise (26 and 24 cases respectively). All patients completed nasal CPAP and (or) aerobic exercise of different intensity for 20 weeks. The therapeutic efficacy of polysomnography (PSG) parameters, glycolipid metabolism, 6 minutes walking distance (6 MWD), and rate of perceived exertion (RPE) were compared between each group before and after treatment. Results: Pre-and post-intervention, PSG parameters, body mass index (BMI) [(26.6±3.7) vs (24.3±2.8) kg/m(2)], RPE [(16.4±1.3) vs (12.2±2.6) score], 6 MWD [(372.6±59.7) vs (441.5±75.6) m] and glucolipid metabolism indexes were improved significantly in nasal CPAP+aerobic exercise group (all P<0.05), such as fasting blood glucose [(7.4±2.4) vs (6.2±1.6) mmol/L], glycosylated hemoglobin [(7.6±1.2)% vs (6.6±0.7)%], fasting insulin [(10.8±4.4) vs (6.9±3.4) µU/L], insulin resistance index [(3.5±1.9) vs (1.9±1.2)], total cholesterol [(4.0±0.9) vs (3.5±0.9) mmol/L], low density lipoprotein cholesterol [(4.2±0.6) vs (3.1±0.8) mmol/L]; BMI, exercise endurance, some glucolipid metabolism indexes and PSG parameters were also improved in aerobic exercise group (P<0.05). After 20 weeks' intervention, it showed statistically significant differences in PSG parameters, glycometabolism, some lipid metabolism indexes and RPE (all P<0.05), and no significantly difference in BMI [(24.3±2.7) vs (24.3±2.8) kg/m(2)] between the two groups. Compared with the low intensity subgroup, there were significant improvement in 2 hours' postprandial insulin, insulin resistance index, low density lipoprotein cholesterol, lipoprotein A, RPE, 6 MWD in moderate subgroup (P<0.05). Conclusion: Nasal CPAP combined with moderate intensity aerobic exercise can effectively improve the glucolipid metabolism, insulin resistance and exercise tolerance in patients with OSAHS and T2DM.

[Predictive value of serum glycosylated hemoglobin for the onset of nonalcoholic fatty liver disease].

Objective: To discuss the affect of glycosylated hemoglobin (HbA1c) level for the onset of nonalcoholic fatty liver disease (NAFLD) in cohort population. Methods: An epidemiological survey of the relationship between HbA1c and NAFLD conducted in 2012 was based at cohort baseline, and three follow-up sessions conducted in 2013, 2014 and 2015. In total 2 811 subjects were included in the study after exclusion of NAFLD patients at baseline and those who lost their lives due to relocation, and death. The Cox proportional hazard model was used to analyze the relationship between glycosylated hemoglobin and other risk factors of NAFLD. Continuous variables were compared using the t-test or the Mann-Whitney test. χ (2)-test was used for the measurement of categorical data. Results: A total of 2 811 subjects with mean age of 59 (58.2±9.8) years old, including 1 664 males and 1 147 females. Age, waist circumference, body mass index, systolic blood pressure, γ-glutamyltransferase and fasting blood glucose level of HbA1c abnormal group were higher than normal group. The incidence of NAFLD in the abnormal HbA1c level group (25.4%) was higher than normal group (14.9 %), and diastolic blood pressure, high-density lipoprotein cholesterol was lower than normal group and the differences were statistically significant. During the three follow-up intervals, there were 440 new cases of NAFLD, consisting 285 males and 155 females with cumulative incidence of 15.7% (440/2 811). Multivariate Cox regression analysis showed that patients with elevated HbA1c had a higher risk of developing NAFLD (HR 1.796; 95% CI 1.335~2.418; P < 0.01), and the increased HbA1c level after adjustment for gender, age, and metabolic syndrome-related factors remained an independent risk factors for NAFLD (HR 1.580; 95.0% CI 1.161-2.152; P < 0.01). Conclusion: An elevated HbA1c levels have a positive predictive value for the onset of NAFLD.

[The correlation between CT score of lung injury and oxygenation index in patients with acute hydrogen sulphide poisoning].

Objective: To explore correlation between chest CT score and oxygenation index in patients with acute hydrogen sulphide poisoning, whether CT score can be applied to assess acute lung injury after acute hydrogen sulfide poisoning and provide basis and reference. Methods: The clinic and a series of CT datas of 32 acute hydrogen sulphide poisoning cases were retrospectively analysed and compared, According to GBZ31-2002 (the diagnostic standard of occupational H(2)S acute poisoning) , these patients were divided into 2 grouds including moderate groud and severe groud; The CT score were improved, referenceing the scoring criteria of the chest X-ray; The difference of the CT score and the oxygenation index were analyzed between moderate and severe group in the acute phase and the disperse phase; The correlation between CT score and oxygenation index were analyzed. Results: The CT score in moderate poisoning group were lower than severe group (2.26±1.37 vs 10.44±2.55, 1.34±0.65 vs 4.55±2.45, all P<0.05) in the acute phase and the dissipation phase.The oxygen index of the 19 cases in the acute phase were 307.55±28.29, and the oxygen index of the 8 cases in the dissipation phase was 435.75±37.00; The oxygen index of the 9 cases in the acute phase and the dissipation phase were respectively 193.17±36.41, 347.67±44.49. The oxygen partial pressure and oxygenation index in severe group were significantly lower than those in moderate group (all P<0.01) in the acute phase and the dissipation phase. Pearman correlation analysis showed that the CT score were negatively correlated to the oxygen index in the acute phase and the dissipation phase, respectively (r=-0.97、-0.75, all P<0.01) . Conclusions: The CT score of lung injury and oxygenation index is negatively correlated. The CT score can be used to evaluate the degree of lung injury, and can be used in the evaluation of acute lung injury after acute hydrogen sulfide poisoning.

Associations between matrix metalloproteinase gene polymorphisms and the development of cerebral infarction.

The aim of this study was to investigate the association between MMP3 rs3025058 and MMP9 rs3918242 polymorphisms and the development of ischemic stroke in a Chinese population. Between May 2013 and January 2015, 335 patients with ischemic stroke and 335 health control subjects were enrolled in this study. The MMP3 rs3025058 and MMP9 rs3918242 polymorphisms were analyzed using polymerase chain reaction coupled with restriction fragment length polymorphism. By multivariate logistic regression analysis, the CC genotype of MMP9 rs3918242 was shown to be associated with a significantly increased risk of ischemic stroke when compared with the TT genotype [OR (95%CI) = 5.47 (2.64-12.38)]. The TC+CC genotype of MMP9 rs3918242 was furthermore found to be associated with an elevated risk of ischemic stroke in higher BMI individuals [OR (95%CI) = 1.81 (1.03-3.22)]. The findings of this study suggest that the MMP9 rs3918242 polymorphism is associated with an elevated risk of ischemic stroke and that this gene polymorphism interacts with BMI in the risk of ischemic stroke.

Development of novel DNA markers for genetic analysis of grey hamsters by cross-species amplification of microsatellites.

The grey hamster has been used in biomedical research for decades. However, effective molecular methods for evaluating the genetic structure of this species are lacking, which hinders its wider usage. In this study, we employed cross-amplification of microsatellite loci of species within the same genus by polymerase chain reaction. Loci screened included 107 from the Mongolian gerbil (MG) and 60 from the Chinese hamster (CH); of these, 15 polymorphic loci were identified for the grey hamster. Of the 167 loci screened, 95 (56.9%) with clear bands on agarose gel were initially identified. After sequencing, 74 (77.9%) of these matched the criteria for microsatellite characteristics, including 41 from MG and 33 from CH. Lastly, 15 (20.3%) loci with more than two alleles for each locus were identified through capillary electrophoresis scanning. To justify the applicability of the 15 grey hamster loci, genetic indexes of grey hamsters were evaluated using 46 generations of outbred stock, established 20 years ago, from Xinjiang, China. Mean effective allele numbers and expected heterozygosity of stock were as low as, respectively, 1.2 and 0.14; these were 2.8 and 4.0 times inferior, respectively, to wild grey hamsters. This finding suggests that the genetic structure of the stock-bred population is too weak to resist artificial and natural selection, mutation and genetic drifting. In conclusion, we have developed de novo microsatellite markers for genetic analysis of the grey hamster, providing data and methodology for the enrichment of a genetic library for this species.

Influence of aggressive nutritional support on growth and development of very low birth weight infants.

AIM: To investigate the influence of the early postnatal aggressive nutritional support on the very low birth weight infants (VLBWI) during hospitalization. MATERIALS AND METHODS: Surviving premature infants without obvious deformity, with gestational age more than 28 weeks and less than 32 weeks, birth weight 1,000 g to 1,500 g, admitted in NICU in Affiliated Children's Hospital of Suzhou University during 12 hours after birth and stay for two weeks or more from January 2008 to December 2011 were selected, including 44 cases (admitted from September 2010 to December 2011) in the observation group and 36 cases in the control group (admitted from January 2008 and September 2010). The infants in the observation group were treated by aggressive nutritional management, while traditional nutritional management for infants in the control group. The variations of nutritional intake, weight gain, jaundice index, blood biochemistry, serum electrolytes indexes, and complications were compared between the two groups. RESULTS: Compared to the control group, the average growth rate and the albumin (ALB) and prealbumin (PA) levels two week after birth and before leaving hospital of the infants in the observation group was significantly higher (p < 0.05), and the incidence of the extrauterine growth retardation was significantly decreasing (p < 0.05). However, the days of hyperbilirubinemia, highest value of the serum bilirubin, duration ofjaundice, platelets after intravenous nutrition, liver function, blood lipid levels, blood glucose, blood PH, serum creatinine, urea nitrogen, and electrolytes of the first day and the seventh day after birth and the in- cidence of parenteral nutrition-associated cholestasis (PNAC) and necrotizing enterocolitis (NEC) between the two group had no difference (p > 0.05). CONCLUSION: The implementation of aggressive nutritional management on the with VLBWI was safe and effective.

Fermi surface nesting induced strong pairing in iron-based superconductors.

The discovery of high-temperature superconductivity in iron pnictides raised the possibility of an unconventional superconducting mechanism in multiband materials. The observation of Fermi-surface (FS)-dependent nodeless superconducting gaps suggested that inter-FS interactions may play a crucial role in superconducting pairing. In the optimally hole-doped Ba(0.6)K(0.4)Fe(2)As(2), the pairing strength is enhanced simultaneously (2Delta/T(c) approximately 7) on the nearly nested FS pockets, i.e., the inner hole-like (alpha) FS and the 2 hybridized electron-like FSs, whereas the pairing remains weak (2Delta/T(c) approximately 3.6) in the poorly nested outer hole-like (beta) FS. Here, we report that in the electron-doped BaFe(1.85)Co(0.15)As(2), the FS nesting condition switches from the alpha to the beta FS due to the opposite size changes for hole- and electron-like FSs upon electron doping. The strong pairing strength (2Delta/T(c) approximately 6) is also found to switch to the nested beta FS, indicating an intimate connection between FS nesting and superconducting pairing, and strongly supporting the inter-FS pairing mechanism in the iron-based superconductors.

A novel missense mutation in GTP cyclohydrolase I (GCH1) gene causes Dopa-responsive dystonia in Chinese Han population.

BACKGROUND: Dopa-responsive dystonia has been shown to be caused by a number of different mutations in the GCH1 gene. Up to now, only several genetic studies of Chinese patients with Dopa-responsive dystonia (DRD) have been reported. METHODS: We performed a genetic analysis by amplifying the entire coding region of GCH1 gene and direct sequencing in four DRD families from mainland China. RESULTS: A novel missense mutation, Gly155Ser, has been identified in a sporadic case from a consanguineous marriage family. Furthermore, two known mutations, Met137Arg and Gly203Arg, have also been detected in the other families. CONCLUSIONS: A novel missense mutation in the GCH1 gene can be associated with DRD. Our findings further expanded the mutational spectrum of GCH1 gene associated with DRD.

The transcription factor Pitx3 is a risk modifier for Parkinson's disease in a Chinese Han population.

BACKGROUND AND PURPOSE: The transcription factor Pitx3 plays a crucial role in the development and survival of midbrain dopaminergic (mDA) neurons, especially the mDA neurons in the substantia nigra pars compacta. The degeneration of these neurons is the pathological hallmark in Parkinson's disease (PD). Several polymorphisms of the Pitx3 gene have been linked with sporadic and early-onset forms of PD, but different studies have given conflicting or inconsistent findings. Amongst the polymorphisms studied, the single-nucleotide polymorphism (SNP) rs3758549, located in the promoter region of Pitx3 gene, is one of the most well-studied but also one of the most controversial. In order to explore the nature of this association in greater detail and in a new ethnic group, we carried out a case-control study of the SNP rs3758549. METHODS: A total of 316 patients with sporadic PD and 305 healthy controls, from two centers in mainland China, were analyzed in our study. The genotypes at rs3758549 were determined by PCR-restriction fragment length polymorphism analysis. And we also analyzed the association between genotype and phenotype. RESULT: Our data showed a significant association between the rs3758549 polymorphism and PD (P = 0.012, OR = 1.50, 95%CI: 1.15-1.96). Furthermore, allele T of SNP rs3758549 was significantly more frequent in early-onset PD than in healthy controls (P < 0.001). CONCLUSION: Our findings indicate that the SNP rs3758549 (C >T substitution) in the Pitx3 gene is a potential risk for sporadic PD, especially early-onset PD in Chinese Han population.