The development and application of a prediction model for postpartum depression: optimizing risk assessment and prevention in the clinic.

BACKGROUND: Preventive intervention can significantly reduce the human and economic costs of postpartum depression (PPD) compared with treatment post-diagnosis. However, identifying women with a high PPD risk and making a judgement as to the benefits of preventive intervention is a major challenge. METHODS: This is a retrospective study of parturients that underwent a cesarean delivery. Control group was used as development cohort and validation cohort to construct the risk prediction model of PPD and determine a risk threshold. Ketamine group and development cohort were used to verify the risk classification of parturients by evaluating whether the incidence of PPD decreased significantly after ketamine treatment in high-risk for PPD population. RESULTS: The AUC for the development cohort and validation cohort of the PPD prediction model were 0.751 (95%CI:0.700-0.802) and 0.748 (95%CI:0.680-0.816), respectively. A threshold of 19% PPD risk probability was determined, with a specificity and sensitivity in the validation cohort are 0.766 and 0.604, respectively. After matching the high-risk group and the low-risk group by propensity score, the results demonstrated that PPD incidence significantly reduced in the high-risk group following ketamine, versus non-ketamine, intervention (p < 0.01). In contrast, intervention in the low-risk group showed no significant difference in PPD outcomes (p > 0.01). LIMITATION: Randomized trials are needed to further verify the feasibility of the model and the thresholds proposed. CONCLUSION: This prediction model developed in this study shows utility in predicting PPD risk. Ketamine intervention significantly lowers PPD incidence in parturients with a risk classification threshold greater than 19%.

The single nucleotide polymorphism Rs12817488 is associated with Parkinson's disease in the Chinese population.

A recent meta-analysis of datasets from five of the published Parkinson's disease (PD) genome-wide association studies implicated the single nucleotide polymorphism (SNP) rs12817488 in coiled-coil domain containing 62 (CCDC62)/huntingtin interacting protein 1 related (HIP1R) as a risk factor for PD. We conducted a case-control study to evaluate the possible association between rs12817488 and PD in Chinese people. All patients (515 PD patients and 518 age and sex-matched controls) were successfully genotyped using polymerase chain reaction restriction fragment length polymorphism analysis. We observed that the rs12817488 polymorphism is associated with PD (p=0.003) and that the genotype and allele frequencies showed a difference between late-onset PD patients and male controls (p=0.025 and p=0.007, respectively). However, there was no difference in the early-onset PD patients and controls. We found a difference in the genotype and allele frequencies between the male PD patients and the male controls (p=0.034 and p=0.017, respectively). However, there was no difference in females. Patients with the A allele were susceptible to PD in both dominant (GA+AA versus GG; odds ratio [OR] 1.365, 95% confidence interval [CI] 1.041-1.788) and recessive (AA versus GG+GA; OR 1.606, 95% CI 1.194-2.158) models. Therefore, our findings support the conclusion that the rs12817488 in CCDC62/HIP1R polymorphism may increase the risk of PD in the Chinese Han population.

Polygenic determinants of Parkinson's disease in a Chinese population.

It has been reported that some single-nucleotide polymorphisms (SNPs) are associated with the risk of Parkinson's disease (PD), but whether a combination of these SNPs would have a stronger association with PD than any individual SNP is unknown. Sixteen SNPs located in the 8 genes and/or loci (SNCA, LRRK2, MAPT, GBA, HLA-DR, BST1, PARK16, and PARK17) were analyzed in a Chinese cohort consisting of 1061 well-characterized PD patients and 1066 control subjects from Central South of Mainland China. We found that Rep1, rs356165, and rs11931074 in SNCA gene; G2385R in LRRK2 gene; rs4698412 in BST1 gene; rs1564282 in PARK17; and L444P in GBA gene were associated with PD with adjustment of sex and age (p < 0.05) in the analysis of 16 variants. PD risk increased when Rep1 and rs11931074, G2385R, rs1564282, rs4698412; rs11931074 and G2385R, rs1564282, rs4698412; G2385R and rs1564282, rs4698412; and rs1564282 and rs4698412 were combined for the association analysis. In addition, PD risk increased cumulatively with the increasing number of variants (odds ratio for carrying 3 variants, 3.494). In summary, we confirmed that Rep1, rs356165, and rs11931074 in SNCA gene, G2385R in LRRK2 gene, rs4698412 in BST1 gene, rs1564282 in PARK17, and L444P in GBA gene have an independent and combined significant association with PD. SNPs in these 4 genes have a cumulative effect with PD.

Association analysis of STK39, MCCC1/LAMP3 and sporadic PD in the Chinese Han population.

With the completion of the Human Genome Project, GWAS have been widely used in exploring the genetic studies of complex diseases. A meta-analysis of datasets from five Parkinson's disease GWAS from the USA and Europe found 11 loci that surpassed the threshold for genome-wide significance (p<5×10(-8)), and five were newly identified loci (ACMSD, STK39, MCCC1/LAMP3, SYT11 and CCDC62/HIP1R). Another GWAS of the Ashkenazi Jewish population also identified loci in STK39 and LAMP3. Because the association between the STK39 and MCCC1/LAMP3 genes and PD was confirmed in different populations, we conducted a case-control cohort to clarify the association between the four single nucleotide polymorphism (SNP) loci (rs2102808 and rs3754775 in the STK39; rs11711441 and rs12493050 in the MCCC1/LAMP3) and PD in the Chinese Han population. Polymerase chain reaction and direct DNA sequencing analyses were used to detect the four variations in a case-control cohort comprised of 993 ethnic Chinese subjects. We found that in the detection of the rs11711441, there was a significant difference between ungrouped populations, early-onset PD, late-onset PD, male PD, female PD and the corresponding control group in allele and genotype frequency (p<0.001, OR<1). In the detection of the rs2102808, rs3754775 and rs12493050, ungrouped populations, early-onset PD, late-onset PD, male PD or female PD with the corresponding control group showed no significant difference in allele and genotype frequency (p>0.0125). Our findings suggested that the allele G of rs11711441 of the MCCC1/LAMP3 gene can decrease the risk of PD in Chinese population. No statistically significant difference in genotype frequency between cases and controls was observed for the other three SNPs.

Hypomethylation of SNCA in blood of patients with sporadic Parkinson's disease.

SNCA is a pathogenic gene identified in rare familial PD, and over-expression of SNCA was suggested in the pathogenesis of familial and sporadic PD. Rep1 polymorphism of SNCA was associated with susceptibility to sporadic PD and SNCA expression in intro and in vivo. Hypomethylation in SNCA intron-1 was associated with increased SNCA expression and was observed in postmortem brains of patients with sporadic PD. We studied the methylation status of SNCA intron-1, SNCA mRNA levels and Rep1 genotypes in PBMCs of 100 sporadic PD patients and 95 controls and explored the relationship between DNA methylation, mRNA expression and Rep1 genotypes. Hypomethylation of SNCA intron-1 was detected in PBMCs of PD patients, and DNA methylation levels were associated with Rep1 polymorphism. The shorter allele was associated with higher level of SNCA intron-1 methylation, and genotypes carrying the shorter allele showed significantly higher methylation level of SNCA intron-1 than genotypes carrying the longer allele. However, SNCA mRNA levels were not associated with disease status, Rep1 polymorphism or DNA methylation of SNCA intron-1 in our study.

Marginal association between SNP rs2046571 of the HAS2 gene and Parkinson's disease in the Chinese female population.

Recent GWASs have implicated many novel SNPs in the development of Parkinson's disease (PD). Single nucleotide polymorphism (SNP) rs2046571 of the HSA2 (encoding hyaluronan synthase 2) was reported to have marginal association with PD. Herein, we conducted a case-control study to evaluate the possible association between SNP rs2046571 and PD in Chinese. All subjects (1043 PD patient and 1044 normal control) were successfully genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. No statistically significant difference in genotype frequency between cases and controls was observed (P=0.074), no statistically significant difference in genotype frequency between early-onset and late-onset was observed (P=0.264 and P=0.120, respectively). No statistically significant difference in genotype frequency between male cases and controls (P=0.108). But surprisingly, there was statistically marginal significant difference in genotype frequency between female cases and controls (P=0.042). Our findings suggested that rs2046571 of the HSA2 has marginal association with PD in Chinese population.

VPS35 gene variants are not associated with Parkinson's disease in the mainland Chinese population.

VPS35 gene mutation has recently been reported in autosomal-dominant, late-onset Parkinson disease (PD). There are no reports regarding the association between VPS35 and Parkinson's disease (PD) in the Chinese population. We conducted a comprehensive genetic analysis of VPS35 gene in a cohort of twenty seven probands belonging to families with autosomal-dominant, late-onset PD, followed up with screening of specific variants in a separate group of 1011 sporadic PD patients and 1016 healthy controls. Our analysis revealed two exonic variants and three intronic variants across the entire VPS35 gene. There was no statistical difference in genotype or allele frequencies of rs3743928 and IVS14-24 t > c variants in VPS35 gene between sporadic PD group and healthy control group. None of the 1011 sporadic PD patients and 1016 controls carried the VPS35 gene c.1858G > A (p.Asp620Asn) mutation. Our data indicated that the VPS35 variants are not associated with PD in the mainland Chinese population.

Association study between two novel single nucleotide polymorphisms and sporadic Parkinson's disease in Chinese Han population.

Two novel single nucleotide polymorphisms (SNPs) (rs6812193 and rs11868035) were recently identified to be associated with Parkinson's disease (PD) in a Web Based Genome-Wide Association Study. Herein, we conducted a case-control study to evaluate the possible associations between these two SNPs and PD in Chinese Han population. All subjects (501 sporadic PD patients and 502 normal controls) were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis with these two SNPs. Chi-square test revealed no significant difference in either genotype frequencies or allele frequencies, even after being stratified by age. But we found that the genotype and allele frequency of rs6812193 shows difference between male patients and male controls (p=0.031, OR=0.584; p=0.037, OR=0.606) but none in the female. Our findings suggest that rs11868035 may have no association with PD in Chinese population and rs6812193 may have marginal association with PD in male Chinese population. However, due to the limited data in the present study, replication studies in larger sample and other populations are required.

Analysis of PLA2G6 gene mutation in sporadic early-onset parkinsonism patients from Chinese population.

Recent studies have shown that PLA2G6 is a causative gene for PARK14-linked autosomal recessive early-onset complicated dystonia-parkinsonism, early-onset parkinsonism with frontotemporal dementia and autosomal recessive early-onset Parkinsonism without added complicated clinical features. In order to investigate the characteristics of PLA2G6 gene mutations in Chinese sporadic early-onset parkinsonism (EOP) patients, we performed polymerase chain reaction and DNA direct sequencing on a cohort of sporadic EOP patients from Chinese population. In this study, we found a novel heterozygous varient (p.G679V). Bioinformatics demonstrates that p.G679V exhibits highly conserved residues across species, which hints it might be a pathogenic mutation. Our result indicated that PLA2G6 mutations might not be a main cause of Chinese sporadic EOP.