MyMedR

Genetic association of AKAP10 gene polymorphism with reduced risk of preterm birth

Langmia IM, Apalasamy YD, Suki SZ, Omar SZ, Mohamed Z

J Perinatol, 2015 Sep;35(9):700-4.

PMID: 26110499 DOI: 10.1038/jp.2015.68

Preterm birth (PTB) is a multifactorial complication in which genetic and environmental factors contribute to the phenotype. The AKAP10 protein encoded by AKAP10 gene has a vital role in the maintenance of myometrial quiescence and pregnancy. This study aimed to investigate whether polymorphisms in the AKAP10 gene are associated with the risk of PTB.

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

Langmia IM, Apalasamy YD, Omar SZ, Mohamed Z

Pharmacogenet Genomics, 2015 Apr;25(4):199-204.

PMID: 25714003 DOI: 10.1097/FPC.0000000000000125

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.

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

Langmia IM, Apalasamy YD, Omar SZ, Mohamed Z

Pharmacogenet Genomics, 2016 Nov;26(11):505-509.

PMID: 27602547

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 1β (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.

Interleukin 1 receptor type 2 gene polymorphism is associated with reduced risk of preterm birth

Langmia IM, Apalasamy YD, Omar SZ, Mohamed Z

J Matern Fetal Neonatal Med, 2015 Dec 23.

PMID: 26607028

Interleukin 1 receptor type 2 (IL1R2) regulates the inflammatory pathway that results in preterm delivery. We aim to investigate the impact of IL1R2 gene polymorphisms on the risk of preterm delivery.

Fulltext Circulating microRNA as a marker for predicting liver disease progression in patients with chronic hepatitis B

Riazalhosseini B, Mohamed R, Apalasamy YD, Langmia IM, Mohamed Z

Rev Soc Bras Med Trop, 2017 Mar-Apr;50(2):161-166.

PMID: 28562750 DOI: 10.1590/0037-8682-0416-2016

INTRODUCTION: Hepatitis B virus (HBV) constitutes an important risk factor for cirrhosis and hepatocellular carcinoma (HCC). The link between circulating microRNAs and HBV has been previously reported, although not as a marker of liver disease progression in chronic hepatitis B (CHB). The aim of this study was to characterize miRNA expression profiles between CHB with and without cirrhosis or HCC.

METHODS:: A total of 12 subjects were recruited in this study. We employed an Affymetrix Gene Chip miRNA 3.0 Array to provide universal miRNA coverage. We compared microRNA expression profiles between CHB with and without cirrhosis/HCC to discover possible prognostic markers associated with the progression of CHB.

RESULTS:: Our results indicated 8 differently expressed microRNAs, of which miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, and miRNA-3200 were up-regulated, whereas miRNA-182 and miRNA-4485 were down-regulated in patients with CHB who progressed to cirrhosis/HCC as compared to those without progression.

CONCLUSIONS:: We demonstrated the differential expression of miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, miRNA-3200, miRNA-182, and miRNA-4485 between patients with HBV without cirrhosis/HCC and those who had progressed to these more severe conditions. These miRNAs may serve as novel and non-invasive prognostic markers for early detection of CHB-infected patients who are at risk of progression to cirrhosis and/or HCC.

Fulltext Progesterone Receptor (PGR) gene polymorphism is associated with susceptibility to preterm birth

Langmia IM, Apalasamy YD, Omar SZ, Mohamed Z

BMC Med Genet, 2015;16:63.

PMID: 26286601 DOI: 10.1186/s12881-015-0202-1

Preterm birth (PTB) is the major cause of death in newborn and the second major cause of death in children less than 5 years old worldwide. Genetic polymorphism has been implicated as a factor for the occurrence of preterm birth. The aim of this study is to evaluate whether polymorphism in the progesterone receptor (PGR) is associated with susceptibility to preterm birth.

Role of pharmacodiagnostic of CYP2C9 variants in the optimization of warfarin therapy in Malaysia: a 6-month follow-up study

Ngow H, Teh LK, Langmia IM, Lee WL, Harun R, Ismail R, et al.

Xenobiotica, 2008 Jun;38(6):641-51.

PMID: 18570163 DOI: 10.1080/00498250801999087

1. A retrospective study was conducted to explore the importance of CYP2C9 genotyping for the initiation and maintenance therapy of warfarin in clinical practice. A total of 191 patients on warfarin therapy in a local hospital were recruited after written informed consent. Their medical records were reviewed and no intervention of warfarin dose was performed. 2. A total of 5 ml of blood were taken from each subject for DNA extraction and identification of 1, 2, 3 and 4 CYP2C9 alleles, using a nested-allele-specific-multiplex-polymerase chain reaction (PCR). Half the patients were Malays and the remaining were Chinese. 3. Two genotypes were detected; 93.2% had CYP2C9 1/1 and 6.8% were CYP2C9 1/3. Warfarin doses were higher in patients with CYP2C91/1. Patients with the 1/3 genotype experienced a higher rate of serious and life-threatening bleeding; 15.4 versus 6.2 per 100 patients per 6 months. 4. The observation clearly highlights the inadequacy of the current dosing regimens and the need to move toward a more individualized approach to warfarin therapy. Prospective clinical studies are now being conducted to assess dosing algorithms that incorporate the contribution of the genotype to allow the individualization of warfarin dose.

Clinical relevance of VKORC1 (G-1639A and C1173T) and CYP2C9*3 among patients on warfarin

Teh LK, Langmia IM, Fazleen Haslinda MH, Ngow HA, Roziah MJ, Harun R, et al.

J Clin Pharm Ther, 2012 Apr;37(2):232-6.

PMID: 21507031 DOI: 10.1111/j.1365-2710.2011.01262.x

Testing for cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) variant alleles is recommended by the FDA for dosing of warfarin. However, dose prediction models derived from data obtained in one population may not be applicable to another. We therefore studied the impact of genetic polymorphisms of CYP2C9 and VKORC1 on warfarin dose requirement in Malaysia.

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