Impact of IL1B gene polymorphisms and interleukin 1B levels on susceptibility to spontaneous preterm birth.

OBJECTIVE: Genetic factors influence susceptibility to preterm birth (PTB) and the immune pathway of PTB that involves the production of cytokines such as interleukins has been implicated in PTB disease. The aim of this study is to investigate the association of interleukin 1ß (IL1B) gene polymorphisms and IL1B levels with spontaneous PTB. STUDY DESIGN: Peripheral maternal blood from 495 women was used for extraction of DNA and genotyping was carried out using the Sequenom MassARRAY platform. Maternal plasma was used to measure IL1B levels. RESULTS: There was no significant association between the allelic and genotype distribution of IL1B single nucleotide polymorphism (SNP) (rs1143634, rs1143627, rs16944) and the risk of PTB among Malaysian Malay women (rs1143634, P=0.722; rs1143627, P=0.543; rs16944, P=0.615). However, IL1B levels were significantly different between women who delivered preterm compared with those who delivered at term (P=0.030); high mean levels were observed among Malay women who delivered at preterm (mean=32.52) compared with term (mean=21.68). IL1B SNPs were not associated with IL1B plasma levels. CONCLUSION: This study indicates a significant association between IL1B levels and reduced risk of PTB among the Malaysian Malay women. This study shows the impact of IL1B levels on susceptibility to PTB disease; however, the high levels of IL1B observed among women in the preterm group are not associated with IL1B SNPs investigated in this study; IL1B high levels may be because of other factors not explored in this study and therefore warrant further investigation.

Association between microRNA-196A2 and microRNA-146A polymorphisms and progression to cirrhosis and hepatocellular carcinoma in patients with viral hepatitis B.

BACKGROUND/AIM: MicroRNAs (miRNAs) are small noncoding RNAs that have been implicated in mechanisms underlying various types of cancers including hepatocellular carcinoma (HCC). Reports have indicated that single nucleotide polymorphisms in miRNA-196A2 and miRNA-146A genes may contribute to the risk of progression of hepatitis B virus (HBV) infection to cirrhosis and HCC. This study aimed to examine the effect of miRNA-196A2 and miRNA-146A polymorphisms on the progression of HBV infection to cirrhosis and/or HCC in HBV patients in the Malaysian population. PATIENTS AND METHODS: This study consists of 423 chronic HBV patients without either cirrhosis or HCC and 103 chronic HBV patients diagnosed with liver cirrhosis or with cirrhosis and HCC. The single nucleotide polymorphisms of miRNA-196A2 (rs12304647 and rs11614913) and miRNA-146A (rs2910164) were genotyped using the Sequenom MassARRAY platform. RESULTS: The genotype distribution in chronic HBV without either cirrhosis or HCC, relative to chronic HBV patients diagnosed with liver cirrhosis or with cirrhosis and HCC revealed that rs12304647 has a protective effect from the development of HCC (odds ratio=0.37, 95% confidence interval=0.15-0.89, P=0.027). However, rs11614913 and rs2910164 were not significantly associated with progression of the HBV infection. CONCLUSION: In summary, rs12304647 is associated with a reduced risk of progression to HCC in patients with chronic HBV infection.

Association of VEGFA gene polymorphisms and VEGFA plasma levels with spontaneous preterm birth.

BACKGROUND: Angiogenic pathway regulating genes such as vascular endothelial growth factor A (VEGFA) have been implicated in preterm birth (PTB) complications. Research shows that the VEGFA/VEGF receptor system plays an important role in the regulation of circulating progesterone level. Attenuation of VEGFA signaling at mid pregnancy results in onset of labor and parturition because of a reduction in circulating progesterone levels. The aim of this study was to investigate the association of VEGFA gene polymorphisms (rs2010963, rs3025039, rs699947, and rs10434) with spontaneous PTB and VEGFA plasma levels in preterm and term women. STUDY DESIGN: Peripheral maternal blood from 495 women was used for extraction of DNA and genotyping was carried out using the SequenomMassARRAY platform. Maternal plasma was used to measure VEGFA levels. RESULTS: Results showed a significant association between rs2010963 variants and PTB at both allelic and genotypic levels. The frequencies of CG and GG genotypes were significantly higher in the preterm group (96%) than in the term group (87%) (P=0.012). The odds of the G allele occurring among the preterm group was 1.8 times higher than those in the term group (odds ratio 1.8, 95% confidence interval 1.2-2.6, P=0.003). After adjustment for Bonferroni correction, the association between rs2010963 variants and PTB remained significant (P=0.004). The rs69947 was associated with PTB at a nominal significance level (P=0.030). There was no significant association between rs3025039, rs10434, and PTB in this population. VEGFA gene polymorphisms were not associated with VEGFA plasma levels. This study indicated for the first time that the VEGFA rs2010963 polymorphisms may play a potential role in preterm complications.