Association of thyroid disease and risk of fatty liver disease: an exposure-wide Mendelian randomization study.

OBJECTIVE: Previous studies have often observed a possible association between thyroid and fatty liver diseases. The pathogenesis of both diseases is complex, with many confounding factors and controversies. We used a two-sample Mendelian randomization (MR) analysis to test the causality between thyroid disease and the risk of developing fatty liver disease. MATERIALS AND METHODS: All data were obtained from the genome-wide association studies (GWAS) Catalog database. Thyroid disorders include hypothyroidism, hyperthyroidism, autoimmune thyroiditis, and Hashimoto's thyroiditis. Fatty liver diseases include alcoholic fatty liver disease and non-alcoholic fatty liver disease (NAFLD). The inverse variance weighting (IVW) method was used for MR analysis, and sensitivity analysis was further performed to test its robustness. RESULTS: We discovered no causal relationship between thyroid disease and alcoholic fatty liver disease after excluding weak instrumental variables (IVs). Hyperthyroidism and hypothyroidism had a significant causal relationship with NAFLD. Hypothyroidism increased the risk of NAFLD using the IVW method (OR=7.62, 95% CI: 2.61-22.25, p<0.001). MR-Egger regression did not suggest potential evidence of directional pleiotropy (intercept, p=0.698). Hyperthyroidism also significantly increased the risk of NAFLD (OR=11.83, 95% CI: 2.9-22.54, p=0.026). MR-Egger regression did not suggest any potential directional pleiotropy (intercept, p=0.295). CONCLUSIONS: Hypothyroidism can significantly increase NAFLD incidence, and hyperthyroidism may be a risk factor for NAFLD.

Risk factors for death from hand-foot-mouth disease: a meta-analysis.

In recent years, outbreaks of hand-foot-mouth disease (HFMD) in China, Singapore and other Western Pacific Region, involving millions of children, have become a big threat to public health. This study aimed to quantitatively assess all qualified studies and identify the risk factors for HFMD death. A systematic search of the databases PubMed, Medline, Embase and the Cochrane Library was performed. Study heterogeneity and publication bias were estimated. Seven case-control studies involving 1641 participants (634 died and 1007 survived) were included in the meta-analysis. Human enterovirus 71 infection, male, age ⩽3 years, vomiting, cyanosis, convulsion, duration of fever ⩾3 days, atypical rashes and abdominal distention were not significantly related to HFMD death (P ⩽ 0.05). Lethargy (odds ratio (OR) = 6.62; 95% CI 3.61-12.14; I2 = 0%; P < 0.0001), pneumonoedema/pneumorrhagia (OR = 4.09; 95% CI 2.44-6.87; I2 = 0%; P < 0.0001), seizures (OR = 6.85; 95% CI 2.37-19.74; I2 = 0%; P = 0.0004), dyspnoea (OR = 8.24; 95% CI 2.05-33.19; I2 = 83%; P = 0.003) and coma (OR = 3.76; 95% CI 1.85-7.67; I2 = 0%; P = 0.0003) were significantly associated with HFMD death, which were risk factors for HFMD death.

Development of polymorphic microsatellites for Meloidogyne incognita, through screening predicted microsatellite loci based on genome sequence.

Microsatellites are extensively distributed in the eukaryotic genome, and they are widely used for their high polymorphism and accessibility. The microsatellites in M. incognita, a worldwide agriculture pest, are inadequate for diversity research. A repertoire of 1620 microsatellites appeared appropriate to design primer as markers were identified based on the M. incognita genome. 120 loci were chosen as candidate, from which 88 microsatellites were characterized. Finally, we found 13 polymorphic microsatellites with 2 to 23 alleles in a survey of three nematode populations in China, while other positive loci were monomorphic. These new molecular markers afford to genetic diversity analysis in M. incognita population of poorly investigation. Furthermore, the predicted microsatellites have potential values for other plant parasitic nematodes.

Chromosomal Mapping and QTL Analysis of Resistance to Downy Mildew in Cucumis sativus.

Downy mildew of cucumber (Cucumis sativus), caused by Pseudoperonospora cubensis, is a major foliar disease worldwide. The cucumber inbred lines K8 (resistant to downy mildew) and K18 (susceptible) were used to study the inheritance of resistance to downy mildew. Chromosomal mapping of the resistance genes was completed to provide a theoretical basis for the resistance mechanisms and for marker assisted selection (MAS). Inoculation was used to test the level of resistance to P. cubensis in the F2 and F2:3 families derived from the cross K8 × K18. Simple sequence repeat (SSR) analysis, combined with bulked segregation analysis (BSA), was done with the DNA of F2 plants using 2,360 pairs of SSR primers. JoinMap Version 3.0 and MapInspect were used to construct SSR linkages and to verify the relationships between these SSR linkages and cucumber chromosomes. Quantitative trait locus (QTL) analysis of downy mildew resistance was done using MapQTL Version 4.0. Inheritance of resistance to downy mildew in K8 was quantitative. Five QTLs for resistance to downy mildew were detected: dm1.1, dm5.1, dm5.2, dm5.3, and dm6.1. The loci of dm1.1 and dm6.1 were on chromosomes 1 and 6, respectively. The loci of dm5.1, dm5.2, and dm5.3 were on chromosome 5, and were linked. Six linked SSR markers for these five QTLs were identified: SSR31116, SSR20705, SSR00772, SSR11012, SSR16882, and SSR16110. Six and four nucleotide binding site (NBS)-type resistance gene analogs (RGAs) were predicted in the region of dm5.2 and dm5.3, respectively. These results will be of benefit for fine-mapping the major QTLs for downy mildew resistance, and for MAS in cucumber.

Prevention of acute and chronic allograft rejection by combinations of tolerogenic dendritic cells.

It is well known that adoptive transfer of donor-derived tolerogenic dendritic cells (DC) helps to reduce acute allograft rejection. However, this method cannot effectively prevent grafts from infiltration of inflammatory cells and fibrosis, and thus has minimal effect on chronic allograft rejection. In this study, we used mitomycin C (MMC) to generate tolerogenic DC and demonstrated that donor (Balb/c)-derived MMC-DC could induce hyporesponsiveness of recipient (C57BL/6) T cells in vitro, potentially by inducing T-cell apoptosis, decreasing IL-2 and IL-12 secretion, and increasing regulatory T-cell numbers and IL-10 secretion. Furthermore, anti-CD154 monoclonal antibody (mAb) treatment combined with donor-derived MMC-DC prolonged the survival of the allografts in vivo. The mechanisms were similar to those in vitro. Impressively, both acute and chronic rejection were prevented when donor and F1 generation (Balb/c × C57BL/6) derived MMC-DC were injected together with anti-CD154 mAb into recipients before heart allotransplantation. In summary, we showed that donor and F1-derived tolerogenic DC have a synergistic effect on induction and maintenance of T-cell regulation and the secretion of immunosuppressive cytokines. Moreover, adoptive transfer of these two types of DC could inhibit both acute and chronic transplant rejection in mice.

Association among interleukin-6 gene polymorphism, diabetes and periodontitis in a Chinese population.

OBJECTIVES: Diabetics significantly increase risk for periodontitis. Interleukin-6 (IL-6) gene polymorphism may play certain roles in the progression of periodontitis with diabetes. The purpose of this study was to assess the association among IL-6 gene polymorphisms, type 2 diabetes mellitus (T2DM) and chronic periodontitis (CP) in a Chinese population. MATERIAL AND METHODS: DNA was obtained from 159 patients with CP, 88 patients with T2DM, 110 patients with CP&T2DM and 135 control subjects. The -174/-572/-597 polymorphisms of IL-6 gene were investigated by restriction fragment length polymorphism of polymerase chain reaction products. The results were further confirmed by sequencing. Significance was set at P < 0.008 after Bonferroni correction. RESULTS: Among four groups, CP&T2DM group showed the lowest IL-6-572 CC genotype and C-allele frequencies (54.5% and 74.1%). In this regard, there were significant differences between CP&T2DM group and the control group [P = 0.006, odds ratio (OR) = 0.475, 95% CI: 0.279-0.808 and P = 0.002, OR = 0.502, 95% CI: 0.319-0.788 respectively]. Logistic regression with adjustment for age, gender, body mass index, smoking and stress showed no significant difference in terms of IL-6-572 genotypes (P = 0.058, OR= 0.523, 95% CI: 0.268-1.022). CONCLUSIONS: The IL-6-572 genotype and allele distributions are unique to subjects with CP&T2DM in a Chinese population.

Genetic variation in the invasive process of Bursaphelenchus xylophilus (Aphelenchida: Aphelenchoididae) and its possible spread routes in China.

Pinewood nematode (Bursaphelenchus xylophilus) is an invasive species that causes a destructive forest disease-pine wilt disease. This disease has been prevalent in some countries in Asia since the 1970s. An amplified fragment length polymorphism survey was used to compare the genetic variation of native and invasive nematode populations in China and to examine the changes in genetic diversity during the invasion process. The genetic diversity of Chinese populations was slightly higher than that of American populations. Analysis of groups sampled from different invasive stages in China, showed that no obvious change in genetic diversity. Hence, genetic drift and founder effects are not obvious in the invasion process. Phylogenetic analysis showed that Chinese pinewood nematode populations were closer to Japanese populations than to American populations. On the basis of the genetic relationships among samples, two major invasion pathways in China are suggested. One is from Guangdong to Anhui and Zhejiang, and the other is from Guangdong to Jiangsu and then from Jiangsu to Hubei, Guizhong and Congqing. The results imply that it is important to reinforce both domestic and international quarantine to control the spread of pinewood nematode.

Immune related genetic polymorphisms and schizophrenia among the Chinese.

Genetic association studies were conducted among two independent cohorts of Chinese ethnicity. The samples consisted of cases and unrelated controls, ascertained from Guangzhou, China, and Singapore. The studies were prompted by our earlier report of an association between schizophrenia and HLA DQB1 alleles (HLA DQB1*0602 and HLA DQB1*0303) in the Singapore sample. Polymorphisms of HLA DQB1 and flanking markers on chromosome 6p21.3 were investigated in the first part of the study. A significant negative association with HLA DQB1*0402 was detected in the Guangzhou sample (Odds ratio, OR 0.26, 95% confidence intervals, CI 0.1, 0.6; p < 0.02, corrected for multiple comparisons). Additional analysis of the Guangzhou and Singapore samples revealed associations at three other anonymous markers flanking HLA DQB1. In the second part of the study, three polymorphisms at the Interleukin-1 gene cluster (IL-1, chromosome 2q13-q21) were investigated in both cohorts, since associations with schizophrenia have been reported in another sample. Persuasive evidence for an association at IL-1 was not detected in either sample. Our results suggest a susceptibility locus for schizophrenia in the HLA region among the Chinese, but further clarification is necessary.

[Effects of 8 years community intervention on risk factors of cardiovascular diseases in Fangshan Beijing].

OBJECTIVE: To study the changes of risk factors of cardiovascular disease in the rural community population after intervention. METHODS: The Beijing Fangshan cardiovascular prevention program was a community-based comprehensive intervention study which was launched from 1991 and ended in 2000 in five communities including three as intervention communities (IC) and two as control communities (CC) in Fangshan, Beijing suburb. The intervention measures were focused on health education and hypertension control. The changes of risk factors of cardiovascular disease in IC and CC were analyzed using random sample in the year 1991, 1995 and 1999, respectively. The risk factors include systolic and diastolic blood pressure (SBP and DBP), body mass index(BMI), serum total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL), smoking, and drinking. RESULTS: From the year 1991 to 1999, the risk factors of cardiovascular disease such as SBP, DBP, smoking rate and drinking rate were reduced in the population of IC. For male in IC, the decline of SBP, DBP, smoking rate, and drinking rate were 1.6 mmHg, 1.1 mmHg, 14.5% (P < 0.01) and 3.7%, respectively. For female of IC, SBP and DBP declined 4.8 mmHg (P < 0.01) and 3.2 mmHg (P < 0.01), respectively. SBP, DBP and smoking rate in the population of CC had a little reduction while BMI, TC and TG increased in both IC and CC. During the period of 1991 to 1999, most cardiovascular risk factors in the population of IC had net reduction compared to that of CC. CONCLUSIONS: Except for BMI and lipids, rural community intervention, as focused on health education and hypertension control, has resulted in the reduction of most risk factors of cardiovascular disease.

[The effect of Beijing Fangshan Cardiovascular Prevention Program on the incidence and mortality of stroke].

OBJECTIVE: To explore potential effective measures for lowering incidence and mortality of stroke in rural community population of China. METHODS: Beijing Fangshan Cardiovascular Prevention Program (BFCP), under whole population and high risk individuals strategies with measures of health education and hypertension control, were launched in 1991 in five communities including intervention communities (IC), about 66,000 residents, and control communities (CC), about 54,000 residents, in Fangshan, Beijing suburb. RESULT: Incidences of stroke averaged 235.23 per 100,000 and 289.22 per 100,000, for IC and CC respectively, with a statistically significant difference, and mortalities of stroke averaged 80.63 per 100,000 and 98.01 per 100,000, for IC and CC respectively, with a statistically significant difference, during years of 1992 to 1999. The net change of stroke incidence was 126.13 per 100,000 in IC versus CC, with a statistically significant difference. Incidences of stroke increased by 11.63% and 75.27%, for IC and CC respectively, while mortalities of stroke decreased by 46.80% and 22.82%, respectively, for IC and CC from years of 1992 to 1999. CONCLUSION: BFCP has yielded obvious effect on controlling incidence and mortality of stroke in rural community population, but the trend of stroke incidence increasing was still not restrained radically.