The association between single nucleotide polymorphism and disease is a typical representation of genetic association studies. Compared with the traditional dichotomous data, single nucleotide polymorphism data has its own characteristics, and 5 genetic models are commonly performed in meta-analysis. In this paper, we show how to use the " meta” package in R software to conduct meta-analysis of single nucleotide polymorphism research through examples.
Objective To investigate the relationship between p53 codon 72 polymorphism and susceptibility to keloid. Methods The p53 genotypes were detected by polymerase chain reactionreverse dot blot(PCRRDB) and DNA direct sequencing among 15 healthy controls and 15 patients with keloid. Results The frequency of the Proallele(P=0.035) and Pro/Pro genotype(P=0.030) in patients was significantly higher than that in the controlls. There was no significant difference in the frequency of Pro/Arg and Arg/Arg genotypes between patients and controls. Conclusion The p53 gene codon 72 polymorphism may play a role in susceptibility to keloid.
Objective To explore the efficacy and safety of the ketogenic diet (KD) in the treatment of genetic developmental and epileptic encephalopathy (DEE). Methods Clinical data from 42 children with genetically confirmed refractory epileptic encephalopathy treated in the Department of Neurology, Jinan Children’s Hospital, between January 2021 and October 2023 were retrospectively analyzed. A classic KD protocol was implemented, and outcomes including seizure frequency, electroencephalogram (EEG) improvement, and adverse reactions were observed at 3, 6, and 12 months post-treatment. Results Among the 42 children, the seizure-free rates at 3, 6, and 12 months of KD treatment were 16.7%, 16.7%, and 14.3%, respectively, while the effective seizure control rates were 69.0%, 52.4%, and 35.7%. At 3 months, comparison of baseline characteristics between the effective and ineffective groups showed no statistically significant differences in gender (P=0.095), age at onset (P=0.648), age at KD initiation(P=0.768), disease duration before KD (P=0.519), presence of abnormal brain MRI findings (P=0.226), epilepsy syndrome classification(P=0.344), or ion channel gene involvement (P=0.066). EEG improvement rates at 6 and 12 months were 54.2% (24 cases) and 42.8% (14 cases), respectively. Retention rates for KD at 3, 6, and 12 months were 100.0%, 71.4%, and 42.8%. Adverse reactions occurred in 7 patients (16.7%), primarily gastrointestinal symptoms (vomiting, constipation, diarrhea; 6 cases) and elevated uric acid (1 case), with no severe adverse events reported. Conclusion KD is an effective treatment for genetic DEE with favorable short-term safety, though long-term adherence requires attention.
Inherited retinal diseases (IRD) are a group of genetic disorders with high genetic and clinical heterogeneity. Patients with IRD may have their clinical diagnosis confirmed by genetic testing. Over the past 30 years, rapid advances in molecular genetics have raised the disease-causing gene variant detection rate and the accuracy of genetic testing, which provide hope to patients. The genetic diagnosis of patients with IRD is complicated due to the overlapping clinical phenotypes, and the fact that different variants lead to different phenotypes and severity even of the same gene. It is very important to overall evaluate the clinical phenotype of patients, precisely select genetic testing methods, and reasonably define disease-causing genes and variants during genetic diagnosis, which can guide the patient's subsequent treatment and provide genetic counseling.
Objective To search for the significant gene indicators in the diagnosis of pancreatic cancer. Methods Literatures about genetic diagnosis of pancreatic cancer were collected and reviewed. Results K-ras, p53, DPC4 and telomerase genes were considered to play important roles in the diagnosis of pancreatic cancer. Conclusion Detection of the genes related to pancreatic cancer may be of helpful in early diagnosis of pancreatic cancer.
Inherited eye disease is a heterogeneous group of eye disorders caused by genetic defects, which has many genetic characteristics, such as multiple inheritance modes and numerous gene variation types. Over the past few decades, genetic testing has improved significantly, with more and more known disease-causing gene variants identified. With the rapid development of high-throughput sequencing technology, clinical diagnosis and treatment of eye genetic diseases have been accelerated, and molecular diagnosis of eye genetic diseases has become an important step in accurate diagnosis and treatment. How to correctly select and evaluate each kind of genetic testing technology, reasonably standardize the use of genetic testing technology, and provide patients with more accurate genetic counseling are problem that clinicians need to seriously consider.
Objective To review the relationshi p between heritable hypercoagulable state (HHCS) and avascular necrosis of femoral head (ANFH). Methods The latest original articles about the relationshi p between HHCS and ANFH were extensively reviewed. Results Several genetic mutations which could cause HHCS, such as thrombophilic factor V G1691A gene, thrombophilic factor II G20210A gene, 5, 10-methylenetetrahydrofolate reductase C677T gene, plasminogen activator inhibitor 1 4G/5G, and tissue factor pathway inhibitor gene, may be genetic risks of ANFH. Conclusion HHCS may be a genetic cause of ANFH. Further studies are needed to confirm the relationship between HHCS and Chinese ANFH.
Objective To summarize the advancement of hereditary thrombophilia. Methods Relevant literatures about hereditary thrombophilia published recently domestic and abroad were reviewed and analyzed. Results The hereditary risk factors of venous thromboembolism were different among different races. In western population, the main risk factors were activated protein C resistance (APC-R) and mutation of factor V Leiden, methylene tetrahydrofolate reductase polymorphism (C677T) and prothrombin G20210A. While in Chinese population, the disorder of protein C system and hyperhomocysteinemia were the major genetic risk factor. The existence of multiple genetic risk factors increased the incidence of primary and recurrent venous thromboembolism. Conclusion Further study on the relations between the hereditary risk factors and thrombophilia will be very important for prediction and prevention of the venous thromboembolism.
ObjectiveTo establish a hereditary deafness genetic screening cohort and conduct prospective follow-up to evaluate the effectiveness of the Nantong newborn genetic deafness screening program. MethodsA study based on traditional screening of newborn hearing was conducted from January 2016 to June 2021. Newborns in six hospitals in Nantong were screened for 15 hotspot mutation loci in four common deafness genes. Cohort follow-up was conducted. ResultsA total of 40 403 newborns were included, with a carrier rate of 39.5 per 1 000 for the four common deafness genes. In total, 168 children with hearing loss (HL) were identified at screening and follow-up, of which 56.5% (95 cases) had severe or very severe HL. The detection rate of HL was significantly higher with combined screening than with traditional screening (3.0‰ vs. 3.9‰, P<0.001). All four carriers of pathogenic mutations with normal hearing developed late-onset HL within 2 years of age. At the end of follow-up, six of the polygenic heterozygous mutation carriers had congenital HL and five had late-onset HL. Carriers of polygenic heterozygous mutations were more common as compared to other carrier mutation populations (2.1% vs. 68.8%, P<0.001). In addition, 525 carriers of the SLC26A4 mutation and 118 carriers of the MT-RNR1 mutation were identified and their parents were counselled during the combined screening, and no children with HL was identified during the follow-up period. ConclusionGenetic screening for deafness improves the detection of HL at birth. It is recommended that carriers of pathogenic mutations with normal hearing at birth be followed up every 3 to 6 months until the age of 2 years. Carriers of polygenic heterozygous mutations should undergo extended screening for deafness genes and have their hearing monitored more intensively for early detection of late-onset or progressive HL.
Objective To summarize results of the correlation of tumor necrosis factor-α (TNF-α) promoter –308A/G polymorphism with systemic lupus erythematosus (SLE) susceptibility in Chinese populations. Methods We collected all the publications about the correlation between TNF-α promoter –308A/G polymorphism and SLE in Chinese populations by searching PubMed, EBSCO, CBM, CNKI and Wanfang Data before the date of March 20, 2010. Meta-analysis was performed for checking the difference between two groups about genotypes such as AA versus GG, GA versus GG, AA versus GG+GA, GA+AA versus GG, and A allele versus G allele. Results A total of 8 studies involving 731 SLE patients and 901 healthy people were included. The meta-analysis of total populations showed that, there was no significant correlation between A allele and increased SLE risk (OR=1.42, 95%CI 0.97 to 2.09, P=0.07); the meta-analyses of populations in different regions showed there was no significant correlation of A allele and increased SLE risk in Chinese Taiwan populations (OR=1.04, 95%CI 0.77 to 1.40, P=0.82). Moreover, there was no significant difference between SLE group and control group in the genotypes of AA versus GG, GA versus GG, AA versus GG+GA, and GA+AA versus GG.Conclusion This meta-analysis dosen’t demonstrate the correlation between TNF-α promoter–308A/G polymorphism and SLE in Chinese populations.