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OBJECTIVES@#Insulin signaling pathway plays an important role in metabolic associated fatty liver disease (MAFLD), however, the association between polymorphisms of genes related to insulin signaling pathway and MAFLD remains unclear. This study aims to investigate the association between insulin signaling pathway-related gene polymorphisms and gene-gene interactions with MAFLD susceptibility in obese children so as to provide scientific basis for further study of genetic mechanism.@*METHODS@#A total of 502 obese children with MAFLD who admitted to Hunan Provincial Children's Hospital from September 2019 to October 2021, were recruited as a case group, and 421 obese children with non-MAFLD admitted during the same period were recruited as a control group. Socio-demographic information, preterm birth history, eating habits, and exercise status of the subjects were collected by inquiry survey, and anthropometric information was collected by physical measurement. At the same time, 2 mL of venous blood was collected to extract DNA, and the polymorphism of insulin signaling pathway-related genes (5 representative candidate genes, 12 variants) was detected. Multivariate Logistic regression analysis was used to investigate the association between insulin signaling pathway-related gene polymorphisms and MAFLD in obese children.@*RESULTS@#After adjusting for confounder factors, INS rs3842748 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 1.749 (1.053 to 2.905), 1.909 (1.115 to 3.267), 1.862 (1.098 to 3.157), all P<0.05]; INS rs3842752 was significantly associated with the risk of MAFLD in obese children in heterozygous and dominant models [OR and 95% CI 1.736 (1.028 to 2.932), 1.700 (1.015 to 2.846), all P<0.05]. NR1H3 rs3758674 was significantly correlated with the risk of MAFLD in obese children in allele model [OR and 95% CI 0.716 (0.514 to 0.997), P<0.05]. SREBP-1c rs2297508 was significantly associated with the risk of MAFLD in obese children in allele and dominant models [OR and 95% CI 0.772 (0.602 to 0.991) and 0.743 (0.557 to 0.991), all P<0.05]. SREBP-1c rs8066560 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 0.759 (0.589 to 0.980), 0.733 (0.541 to 0.992), 0.727 (0.543 to 0.974), all P<0.05]. NR1H3 rs3758674 mutant C and SREBP-1c rs2297508 mutant G had interaction in the development of MAFLD in obese children [OR and 95% CI 0.407 (0.173 to 0.954), P<0.05].@*CONCLUSIONS@#The INS, NR1H3, and SREBP-1c gene polymorphisms in the insulin signaling pathway are associated with the susceptibility of MAFLD in obese children, but the functions and mechanisms of these genes need to be further studied.
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Child , Infant, Newborn , Humans , Female , Pediatric Obesity/genetics , Sterol Regulatory Element Binding Protein 1 , Premature Birth , Non-alcoholic Fatty Liver Disease , Signal Transduction/genetics , InsulinsABSTRACT
Objective:To understand the distribution and epidemiological characteristics of chronic lymphocytic leukemia (CLL) in Hunan Province.Methods:According to the audit methods and evaluation criteria specified by the National Cancer Registration Center, the registration data of CLL reported by 24 tumor registries was included. Through the research method of retrospective analysis, the selected registry data was calculated and analyzed according to the year, administrative division, urban and rural areas, gender and age.Results:A total of 104 newly diagnosed CLL patients were diagnosed in Hunan Province from 2014 to 2015, with an average annual morbidity of 0.39/100, 000. The morbidity in 2014 and 2015 was 0.39/100, 000 and 0.39/100, 000, respectively. The annual average morbidity in Zhuzhou was 0.8/100, 000, which was the highest among municipalities. The annual average morbidity in Kaifu District of Changsha was 1.65/100, 000, which was the highest among district-level administrative divisions. The morbidity of urban was higher than that of rural (Urban vs Rural, P=0.006). The male to female morbidity was 1.7∶1. The cases were mainly concentrated in the 61-70-year-old population, accounting for 33.65% of all cases (35/104). There were 64 patients died of CLL in Hunan Province from 2014 to 2015, and the average annual mortality was 0.24/100, 000. The mortality in 2014 and 2015 was 0.22/100, 000 and 0.26/100, 000, respectively. The average annual mortality in Hengyang was 0.53/100, 000, which was the highest among municipalities. The average annual mortality in Furong District of Changsha was 0.74/100, 000, which was the highest among district-level administrative divisions. The mortality of urban was higher than that of rural but with no significant difference ( P=0.006). The male to female mortality rate was 1.4∶1. The deaths were mainly concentrated in the 71-80-year-old population, accounting for 29.69% of all deaths (19/64). Conclusions:The morbidity of CLL in Hunan Province is much lower than that of European and American populations, and it mainly occurs in the elderly people. It is more common in men. The morbidity of urban is higher than that of rural and morbidity in Zhuzhou is the highest. The death of CLL patients was mainly in middle-aged and elderly population, with more males. The mortality of urban is slightly higher than that of rural and the mortality in Hengyang is the highest.
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Purpose@#Inflammatory cytokines are thought to be involved in the pathogenesis of intracranial aneurysm (IA), although resultsamong studies in the literature are inconsistent. This article sought to review studies on the associations among polymorphismsin inflammatory cytokine genes and IA risk and to provide recommendations for future research. @*Materials and Methods@#A systematic search of PubMed, Embase, and Web of Science was conducted up to August 4, 2019. Theassociations between polymorphisms of inflammatory cytokine genes and IA risk were estimated by pooled odds ratios (ORs) and95% confidence intervals (CIs). Subgroup analyses were performed according to race. Qualitative systematic review was conductedfor variants that were studied in only one study. All analyses were performed using STATA 12.0. @*Results@#13 studies investigating the associations between polymorphisms in five inflammatory cytokine genes (TNF-α, IL-1α, IL-1β, IL6, and IL-12B) and IA were reviewed. Combined results showed that the A allele of TNF-α rs1800629 polymorphism has aprotective effect against IA (dominant model: OR=0.65, 95% CI=0.47–0.89, p=0.007). No associations were identified between polymorphismsin IL-1α rs1800587, IL-1β rs16944, IL6 rs1800795 and rs1800796, or IL-12B rs3212227 and IA risk. @*Conclusion@#This review demonstrated an association between TNF-α rs1800629 polymorphism and IA in Caucasians, illustratingthe potentially important role of genes involved in inflammation in IA.
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The subarachnoid hemorrhage (SAH) caused by ruptured intracranial aneurysms (IAs) is always a lethality. Increasing evidence suggests a familiar aggregation of IA occurrence, which may relate to genetics and there might be an increasing number of IAs in IA families when mutation of disease genes is aggregating. With the progress in the study of familiar intracranial aneurysms (FIAs), a large number of chromosome fragments are found to be related with IAs, such as 1p36, 5q31, 7q11, 14q22, 17cen, 19q13, Xp22. Further studies indicated that mutation of several genes could be the cause of FIAs, including TNFRSF13B, ANRIL, SOX17, ADAMTS15, RNF213 and LOXL2. The independent genetic epidemiologic study on aneurysm families can be used to discover the related genes more effectively, and to explore the mechanism of occurrence of IAs. It's also the precondition for the prevention of disease.
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Humans , Adenosine Triphosphatases , Amino Acid Oxidoreductases , Genetic Research , Intracranial Aneurysm , Genetics , Risk Factors , Ubiquitin-Protein LigasesABSTRACT
PURPOSE: Genome-wide association studies (GWAS) have revealed that common variants on or near EDNRA, HDAC9, SOX17, RP1, CDKN2B-AS1, and RBBP8 genes are associated with intracranial aneurysm (IA) in European or Japanese populations. However, due to population heterogeneity, whether these loci are associated with IA pathogenesis in Chinese individuals is still unknown. The purpose of this study was to investigate associations among GWAS-identified loci and risk of IA in a Chinese population. MATERIALS AND METHODS: A total of 765 individuals (including 230 IA patients and 535 controls) were involved in this study. Twelve single nucleotide polymorphisms (SNPs) of candidate loci were genotyped using the Sequenom MassARRAY platform. Associations were analyzed using univariate or multivariate logistic regression analysis. RESULTS: SNPs in CDKN2B-AS1 (especially rs10757272) showed significant associations with IA in dominant and additive models [odds ratio (OR), 2.99 and 1.43; 95% confidence interval (CI), 1.44–6.24 and 1.10–1.86, respectively]. A SNP near HDAC9 (rs10230207) was associated with IA in the dominant model (OR, 1.42; 95% CI, 1.01–1.99). One SNP near RP1 (rs1072737) showed a protective effect on IA in the dominant model (OR, 0.66; 95% CI, 0.46–0.95), while another SNP in RP1 (rs9298506) showed a risk effect on IA in a recessive model (OR, 3.82; 95% CI, 1.84–7.91). No associations were observed among common variants near EDNRA, SOX17, or RBBP8 and IA. CONCLUSION: These data partially confirmed earlier results and showed that variants in CDKN2B-AS1, RP1, and HDAC9 could be genetic susceptibility factors for IA in a Chinese population.
Subject(s)
Humans , Asian People , Genetic Predisposition to Disease , Genome-Wide Association Study , Intracranial Aneurysm , Logistic Models , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Population CharacteristicsABSTRACT
In the past decade,based on the “common disease-common variant” hypothesis,genomewide association studies (GWAS) have been extensively used to dissect the genetic components of complex diseases and quantitative traits.However,the identified disease-associated common variants by GWASs can only explain small part of the corresponding disease heritability.“Common disease-rare variant” hypothesis has been proposed to explore the missed heritability.With the development of the next generation sequencing technology,various association studies of less common variants are ongoing.This paper provides an overview of the study designs and statistical tests of these variants.
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In the past decade,based on the “common disease-common variant” hypothesis,genomewide association studies (GWAS) have been extensively used to dissect the genetic components of complex diseases and quantitative traits.However,the identified disease-associated common variants by GWASs can only explain small part of the corresponding disease heritability.“Common disease-rare variant” hypothesis has been proposed to explore the missed heritability.With the development of the next generation sequencing technology,various association studies of less common variants are ongoing.This paper provides an overview of the study designs and statistical tests of these variants.
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Objective To investigate the correlation between RNF213 gene polymorphisms (rs112735431,rs138130613,and rs148731719) and the susceptibility of intracranial vascular stenosis disease.Methods The literature of studies on the correlation between RNF213 gene polymorphisms and intracranial vascular stenosis disease was collected according to the related databases.Using the Stata 12.0 software and selecting suitable genetic model,the heterogeneity was analyzed and the pooled odds ratio (OR) and its 95％ confidence interval (CI) were calculated.Results A total of 12 articles were included after screening.The result of meta-analysis showed that the rs112735431 polymorphism had a significant correlation with the susceptibility of moyamoya disease (MMD) in all genetic models,especially the most significant dominant model (AA + GA genotype vs.GG genotype:OR 101.46,95％ CI 59.41-173.27;P ＜0.001),at the same time,the polymorphism of this site also had significant correlation with the nonMMD intracranial large artery stenosis/occlusion (AA + GA genotype vs.GG genotype:OR 13.82,95％ CI 4.48-42.61;P＜ 0.001);the rs138130613 polymorphism had significant correlation with the susceptibility of MMD in Chinese population (OR 5.01,95％ CI 1.57-15.98;P=0.006);and no correlation between the rs148731719 polymorphism and the susceptibility of MMD was observed.Conclusions The RNF213 gene rs112735431 polymorphism is a susceptible factor of MMD,at the same time,the polymorphism of this site is also associated with the formation of non-MMD intracranial large artery stenosis.Systematic study on the molecular function of RNF213 may have important significance for diagnosis and treatment of such vascular stenosis diseases.
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Objective To analyze risk factors for metabolic syndrome in Mongolia versus Han nationalities in Xilinhaote city. Methods Using the epidemiology investigation data of health examination,we calculated the prevalence of metabolic syndrome of Mongolia and Han nationalities, then used logistic regression model to explore risk factors of two nationalities. Results The crude prevalence of MS in Mongolia and Han nationality was 34.3%and 24.6% respectively. The multivariate logistic regression showed that male, the meat-rich diets and aging(OR:2.18, 1.92, 1.04 respectively)were the risk factors for Mongolia nationality, and smoking, family history of hypertension, drinking, the meat-rich diets, aging(OR:1.89, 1.84, 1.72, 1.61 and 1.04 respectively)were the risk factors for Han nationality. Conclusions Xinlinhaote population has higher MS prevalence, and different nationalities have different risk factors. We should take preventive actions to control it.
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Objective To compare the differences of three diagnostic criterions for metabolic syndrome (MS) proposed by the International Diabetes Federation (IDF) in 2005, the Third Report of National Cholesterol Education Program-Adult Treatment Panel Ⅲ (NCEP-ATPⅢ) in 2005 and Chinese Diabetes Society(CDS)in 2004 in population of Xilinguole city in inner mongolia. Methods 1 060 employees aged more than 20 yrs in enterprises taken health examination in Xilinguole hospital were investigated by epidemiological survey and the prevalence rates of MS and its components were calculated according to these three definitions respectively, and compared the agreement rates and difference between these definitions. Results The age-adjusted MS prevalence rates were 25.0%, 27.9% and 22.5% according to IDF (2005), ATPⅢ (2005) and CDS (2004) respectively. The agreement rate of diagnosis between IDF and ATPⅢ was the highest, and the Kappa value was 0.929. The kappa values between IDF and CDS,ATPⅢ and CDS were 0.726 and 0.763, respectively. There were 4.3% and 10.8% subjects respectively without MS diagnosed by IDF and CDS criterion presented at least 3 risk factors respectively. For Mongolia nationality people, when the waist circumference was 90cm in male and BMI was 25kg/m2 in female, the sensitivity and specificity were relative better, and the distance of ROC curve was the shortest, but for Han nationality, BMI≥25 kg / m2 in male and waist circumference ≥80 cm was better. Conclusion ATPⅢ definition can screen out the highest prevalence of MS and risk factors aggregation among three definitions, and it's best for screening for the high risk population of cardio-cerebrovascular diseases. The cutoff value of waist circumference (WC) in IDF and ATP Ⅲ seems better for Mongolia nationality men; while the cutoff value in CDS was better for Han nationality men. We should combine waist circumference and body mass index to judge the condition of obesity.