Association analysis of the DISC1 gene with schizophrenia in the Japanese population and DISC1 immunoreactivity in the postmortem brain

The Disrupted-in-Schizophrenia 1 (DISC1) gene plays a role in the regulation of neural development. Previous evidence from genetic association and biological studies implicates the DISC1 gene as having a role in the pathophysiology of schizophrenia. In the present study, we explored the association between DISC1 missense mutation rs821616 (Ser704Cys) single nucleotide polymorphism (SNP) and four other SNPs (rs1772702, rs1754603, rs821621, rs821624) in the related haplotype block and schizophrenia in the Japanese population. We could not find a significant association of selected SNPs with schizophrenia after correction for multiple testing. We performed a meta-analysis of the Ser704Cys variant in schizophrenia using data from the present study and five previous Japanese population studies, and found no association with schizophrenia. We also examined DISC1 immunoreactivity in postmortem prefrontal cortex specimens of schizophrenia patients compared to control samples. The immunoreactivity revealed a significant decrease of DISC1 protein expression in the schizophrenia samples after ruling out potential confounding factors. However, the Ser704Cys variant did not show effects on DISC1 immunoreactivity. These results provide evidence that this functional genetic variation of DISC1 do not underlie the pathophysiology of schizophrenia in the Japanese population.     

Factors associated with the age of natural menopause and menopausal symptoms in Chinese women

Objective

To investigate the factors associated with the age of natural menopause and menopausal symptoms in a large population of Chinese middle-aged women.

Study design

In this cross-sectional study, a total of 20,275 women (40–65 years) attending health screening in Jiangsu Province of China were enrolled. A structured questionnaire was used to collect data of demographics, menopausal status, chronic diseases, reproductive history, etc. Also we evaluated the severity of menopausal symptoms by Kupperman menopause index (KMI).

Main outcome measure

Menopausal age and scorings of Kupperman menopause index.

Results

The overall median age at natural menopause was 50 years. Lower educational level, poor economic status, lower body mass index (BMI), age at menarche less than 14 years, nulliparity and smoking were associated with earlier onset of natural menopause (P < 0.05). The most frequently symptoms in postmenopausal women were sexual problems (57.05%), muscle/joint pain (53.29%) and insomnia (51.02%), while fatigue, insomnia and muscle/joint pain were predominant symptoms in pre- and peri-menopausal women. After adjusting for confounding factors, logistic regression analysis revealed that women with poor educational background, low income, divorce, higher BMI, higher parity, smoking and chronic diseases presented higher KMI scores (P < 0.05).

Conclusion

The study provided an estimate of median age at natural menopause in Chinese women. The main factors contributing to earlier onset of menopause and severity of menopausal symptoms were lower educational level, poor economic status, and smoking. Thus, this study provides important insights for physicians to prevent and treat menopause related symptoms.     

Haplotypes of the IL-1 gene cluster are associated with gastroesophageal reflux disease and Barrett’s esophagus

Objectives

Gastroesophageal reflux (GERD) is a one of the major public health problem that can lead to reflux esophagitis (RE), Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC). The aim of our study was to determine the impact of IL-1 gene polymorphisms on the development of GERD, RE and BE.

Methods

Three hundred and thirty-three Czech patients with gastroesophageal reflux and 165 healthy controls were included in this case-control study. Four polymorphisms in the genes of the IL-1 cluster [IL-1A(-889C/T), IL-1B(−511C/T), IL-1B(+3953C/T), and IL-1RN(VNTR)] were analyzed.

Results

Significant differences were found in IL-1RN 1/2 genotype between patients with GERD/RE and controls and in IL-1B+3953 T allele between patients with BE and healthy subjects. In addition, complex analysis revealed differences in IL-1 haplotype frequencies between the groups. Specifically, the haplotype TCCL was significantly more frequent (p = 0.016) in GERD patients than in controls and the haplotype CCCL more frequent (p = 0.008) in RE patients than in controls. However, in patients with BE, frequency of haplotype TCTL was lower (p = 0.05) and haplotypes CTCL and TCCL were higher (p = 0.03 and p = 0.02) in comparison with the controls.

Conclusions

Our results suggest that IL-1 haplotypes may be associated with susceptibility to GERD, RE and BE.     

Genetic study confirms association of HLA-DPA101:03 subtype with ankylosing spondylitis in HLA-B27-positive populations

The association of human leukocyte antigen (HLA)-B27 with ankylosing spondylitis (AS) has been known for over 38 years. However, it is not the only gene associated with AS. The aim of this study was to confirm the association of HLA markers around HLA-DPA1/DPB1 region with AS in HLA-B27 positive populations. Five SNPs (rs422544, rs6914849, rs92777535, rs3128968 and rs2295119) from the HLA-DPA1/DPB1 region were genotyped in 340 individuals HLA-B27-positive from Portugal (137 AS patients and 203 healthy controls). Characterizations of HLA-DPA1/DPB1 alleles were also performed. rs422544 revealed a significant association with AS (P < 0.05) and sliding windows (SW) analysis showed association of some groups of adjacent SNPs within HLA-DPA1/DPB1 region with AS (P < 0.05). We also found association of the HLA-DPA1^∗01:03 allele with AS (P < 0.05). This is the first study that confirms the association of HLA markers and haplotypes around HLA-DPA1 and HLA-DPB1 with AS.     

PADI4 polymorphisms and the functional haplotype are associated with increased rheumatoid arthritis susceptibility: A replication study in a Southern Mexican population

Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The peptidyl arginine deiminase type IV (PADI4) gene has been associated with RA susceptibility in several populations. We addressed the relationship between three exonic PADI4 gene single nucleotide polymorphisms (SNPs) PADI4_89 (rs11203366), PADI4_90 (rs11203367) and PADI4_92 (rs874881) and related haplotypes with RA in a population from Southern México. This study included 200 RA patients and 200 control subjects. The SNPs were evaluated using the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) technique, and antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). In this population, the minor alleles of PADI4_891G, PADI4_901T and PADI4_921G gene polymorphisms were associated with RA susceptibility (OR = 1.34, p = 0.04; OR = 1.35, p = 0.03; OR = 1.34, p = 0.04; respectively). The GTG haplotype was also significantly associated with RA (OR = 2.27 95%CI = 1.18–4.41; p = 0.008), but did not show association with levels of anti-CCP antibodies and clinical parameters. In conclusion, our replication study in a Southern Mexican population suggests that PADI4 individual polymorphisms and the related susceptibility haplotype (GTG) are also genetic risk markers for RA.