ABSTRACT. CDKAL1 (cyckin-dependent kinase 5 regulatory subunitassociated protein 1-like 1) has been shown to be associated with type 2 diabetes in various ethnic groups; however, contradictory results have been reported. We performed a comprehensive meta-analysis of 21 studies for rs7756992, 17 studies for rs7754840 and 10 studies for rs10946398 variants of the CDKAL1 gene to evaluate the effect of CDKAL1 on genetic susceptibility for type 2 diabetes. We found a significant association of rs7756992, rs7754840 and rs10946398 in CDKAL1 with type 2 diabetes (odds ratio (OR) = 1.15, 95% confidence interval (CI) = 1.07-1.23, P < 0.0001; OR = 1.14, 95%CI = 1.06-1.24, P = 0.001, and OR = 1.12, 95%CI = 1.07-1.18, P < 0.0001, respectively). We conclude that there are significant associations between CDKAL1 polymorphisms and type 2 diabetes, but these associations vary in different ethnic populations.

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Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) expressing microRNAs have been highlighted in human diseases. However, the detailed molecular mechanism of hucMSCs-derived exosomal miR-18b-3p on preeclampsia (PE) remains further investigation. We aimed to investigate the effect of exosomes and miR-18b-3p/leptin (LEP) on occurrence of PE. The morphology of the hucMSC and hucMSC-exosomes (Exos) was identified. The exosomes were infected with different lentivirus expressing miR-18b-3p to explore the role of miR-18b-3p in PE. The PE rat model was established by intraperitoneal injection of N-nitro-l-arginine methyl ester. The expression of LEP and miR-18b-3p was tested in PE rat placenta tissues. Also, the effect of exosomes on LEP and miR-18b-3p expression was detected. The systolic blood pressure (SBP), proteinuria, inflammatory factors, the weight of fetal rat and placenta and cell apoptosis in PE rats were detected. Finally, the relationship between miR-18b-3p and LEP was verified using dual-luciferase reporter gene assay and RNA pull-down assay. Exosomes, restoring miR-18b-3p or inhibiting LEP reduced SBP and proteinuria of PE rats as well as increased the weight of fetal rat and placenta, decreased serum levels of inflammatory factors as well as suppressed apoptotic cells of PE rats, exerting a suppressive effect on PE progression. miR-18b-3p was decreased and LEP was increased in placenta tissues of PE rats. LEP was the direct target gene of miR-18b-3p. Upregulation of miR-18b-3p or treatment of the exosomes suppressed LEP expression and reduced PE occurrence, while downregulation of miR-18b-3p had contrary effects. Downregulated LEP reversed the effect of miR-18b-3p reduction on PE rats. HucMSCs-derived exosomal miR-18b-3p targets LEP to participate in the occurrence and development of PE. This study may provide a novel theoretical basis for the mechanism and investigation of PE.

Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries. The relationship between genetic polymorphisms and the risk of cancers has been widely researched. Excision repair cross-complementing group 2 (ERCC2) gene plays important roles in the nucleotide excision repair pathway. There is contrasting evidence on the association between the ERCC2 Asp312Asn polymorphism and the risk of cancer. We conducted a comprehensive meta-analysis in order to assess the correlation between these factors. We searched the PubMed, EMBASE, Science Direct, Web of Science, and CNKI databases for studies published from January 1, 2005 to January 1, 2016. Finally, 86 articles with 38,848 cases and 48,928 controls were included in the analysis. The overall analysis suggested a significant association between the ERCC2 Asp312Asn polymorphism and cancer risk. Furthermore, control source, ethnicity, genotyping method, and cancer type were used for subgroup analysis. The result of a trial sequential analysis indicated that the cumulative evidence is adequate; hence, further trials were unnecessary in the overall analysis for homozygote comparison. In summary, our results suggested that ERCC2 Asp312Asn polymorphism is associated with increased cancer risk. A significantly increased cancer risk was observed in Asian populations, but not in Caucasian populations. Furthermore, the ERCC2 Asp312Asn polymorphism is associated with bladder, esophageal, and gastric cancers, but not with breast, head and neck, lung, prostate, and skin cancers, and non-Hodgkin lymphoma. Further multi-center, well-designed studies are required to validate our results.

Huang Q, Ding W, Wei MX. Comparative analysis of common CFTR polymorphisms poly-T, TG-repeats and M470V in a healthy Chinese population. World J Gastroenterol 2008; 14(12): 1925-1930 INTRODUCTIONThe cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7q31 spans approximately 250 kb of DNA and encodes 27 exons encodes [1] . The CFTR gene encodes a cAMP-and ATP-dependent chloride channel that is present in the apical membrane of the epithelial cells that line most exocrine glands [2] . Phosphorylation of the regulatory domain by protein kinase A, followed by binding and hydrolysis of ATP at both nucleotide-binding domains, regulates the transport of chloride ions through the channel [3] . Absence, reduced levels, or malfunction of the CFTR protein results in cystic fibrosis (CF), and CF-like diseases such as congenital bilateral absence of the vas deferens (CBAVD) [4,5] , bronchiectasis [6] and chronic pancreatitis [7] . Since the discovery of the CFTR gene, more than 1000 mutations and 200 polymorphisms have been identified [8] . CF is one of the most common autosomal recessive disorders in Caucasians, with an incidence of approximately 1 in 2500 Caucasian births and a carrier frequency of approximately 1 in 25. However, in Asians, the prevalence of CF is very low, with an incidence of approximately 1 in 100 000, and in particular, the severe mutations, such as ∆F508, G542X and N1303K, are rarely found in Asians. Previous studies have demonstrated that polymorphisms outside the CFTR gene [9,10] , as well as within the gene, may affect transcription or function of the CFTR protein and modify the phenotype of some CF mutations. It has been mentioned that poly-T, TG-repeats and M470V polymorphisms play a role in the development of CF-like diseases. The poly-T tract located at the junction of intron Abstract AIM: To investigate the three important cystic fibrosis transmembrane conductance regulator (CFTR ) haplotypes poly-T, TG-repeats and the M470V polymorphisms in the Chinese population, and to compare their distribution with that in Caucasians and other Asian populations. RAPID COMMUNICATION METHODS:Genomic DNA was extracted from blood leukocytes. Exons 9 and 10 of the CFTR gene were obtained through polymerase chain reaction (PCR). Exon 9 DNA sequences were directly detected by an automated sequencer and poly-T and TG-repeats were identified by direct sequence analysis. Pure exon 10 PCRamplified products were digested by Hph Ⅰ restriction enzyme and the M470V mutation was detected by the AGE photos of digestion products.RESULTS: T7 was the most common (93.6%) haplotype and the (TG)11 frequency of 57.2% and (TG)12 frequency of 40.9% were dominant haplotypes in the junction of intron 8 (IVS-8) and exon 9. The frequency of T5 was 3.8% and all T5 allele tracts (10 alleles) were joined with (TG)12. Four new alleles of T6 (1.5%) were found in three healthy individuals. In exon 10, the V allele (56.1%) was slightly more frequent than the M allele (43.9%), and the M/V (45.5%) was the dominan...

Autophagy acts as a double-edged sword in cancer. Over the years, there has been growing evidence of the involvement of autophagy-related genes (ATGs) in the etiology and progression of cancer. Importantly, lung cancer is one of the most common cancers and represents the leading cause of cancer-related mortality in developing countries. The genomic variant has emerged as an important factor in the risk of lung cancer. Here, we hypothesize that the intron single-nucleotide polymorphism (SNP) of rs807185 in ATG4A is associated with the risk of lung cancer. In this case-control study, we genotyped the SNP rs807185 with PCR-restriction fragment length polymorphism. Our data suggest that the variant A allele frequency of rs807185 in controls is higher than that in cases (37.7 vs. 24.9%, P=0.006). The adjusted odds ratio is 1.989 (95% confidence interval 1.223-3.236). Compared with the wild T allele, the variant A allele of rs807185 in ATG4A is associated with a decreased risk of lung cancer (adjusted odds ratio=0.605, 95% confidence interval 0.456-0.803, P<0.001). Furthermore, stratified analysis in a recessive model suggests that the homozygous variant genotype (AA) of rs807185 could decrease the risk of lung cancer in smoking or nonsmoking groups. In conclusion, the variant of intron SNP rs807185 in ATG4A is associated significantly with a decreased risk of lung cancer in a southwest Chinese population. The results show that the variant rs807185 of ATG4A might be a protective factor for lung cancer.

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Roles of interleukin-31 (IL-31) in the development and progression of human epithelial ovarian cancer are largely unknown. Studies report that the polymorphisms, rs7977932 C>G and rs4758680 C>A in IL-31, affect the expression level of IL-31. In the present study, we examined 412 patients with epithelial ovarian cancer and 428 healthy individuals to explore whether these polymorphisms are associated with the epithelial ovarian cancer in Chinese women. The genotype of the polymorphisms in each individual was identified. The associations of the polymorphisms with patients' clinical characteristics and outcomes were evaluated. For rs7977932, the frequency of the CG/GG was significantly decreased in patients with epithelial ovarian cancer. However, the frequency of the rs4758680 CA/AA was significantly increased in those patients. Moreover, the frequency of rs7977932 CG/GG genotype was significantly higher in patients with less advanced FIGO stages. Kaplan-Meier curve showed that patients with CG/GG genotypes of rs7977932 had a decreased risk for recurrence compared to those with CC genotype. Our findings suggested that rs7977932 and rs4758680 of IL-31 may be associated with the development and progression of the epithelial ovarian cancer in the Chinese population. IL-31, therefore, may be a potential therapeutic target for the development of drugs to treat the disease.