Factors influencing circulating microRNAs as biomarkers for liver diseases.

MicroRNAs (microRNAs) have been implicated to play crucial roles in various liver diseases. Hepatic microRNAs are released in to the circulation in a systematic fashion, and are, therefore, being extensively explored for their role as prognostic or diagnostic markers or therapeutic targets for numerous hepatic diseases. Advantages such as disease- or tissue-specific expression, and ease of detection have implicated circulating microRNAs (c-microRNAs) as the most desirable candidate for biomarker studies. Although several studies have explored c-microRNAs in serum or plasma, consistency of detection of microRNAs remains demanding because of many biological and methodological challenges. Lack of methodological consensus has limited the universal use of c-microRNAs as potential prognostic or diagnostic disease-specific biomarkers. In this review, we have discussed pre-analytical and analytical factors that might affect c-miRNA expression and selection of appropriate data normalization strategy by incorporating endogenous reference microRNAs. This review will aid designing of better approaches and protocols for future diagnostic research on hepatic c-microRNAs.

Association of Genetic Variants with Hyperhomocysteinemia in Indian Patients with Thrombosis.

Hyperhomocysteinemia known to be associated with increased thrombotic tendency has been considered as a risk factor for coronary artery disease, atherosclerosis, venous thrombosis, and stroke. There are three main genes MTHFR, cystathionine beta-synthase (CBS) and methionine synthase (MS) and it's genetic variant that are known to influence the homocysteine metabolism leading to hyperhomocysteinemia. There is scarcity of Indian data on hyperhomocysteinemia and genetics variants in patients with thrombosis. Hence the objective of present study was to determine MTHFR, CBS, and MS genetic variants in thrombosis patients from Indian population. Genetic variant analysis was performed on thrombosis patients to detect MTHFR C677T (rs1801133), MTHFR A1298C (rs1801131), MS A2756G (rs1805087) and CBS T833C (rs5742905) mutations. The mutant allele frequencies of MTHFR 677T, MTHFR 1298C, MS2756G and CBS 833C were observed to be 16.1%, 37.5%, 34.1% and 5.8% respectively. MTHFR 677TT genotype was observed to be significantly associated with elevated homocysteine (Hcy) levels (64.65 µmol/L) alleles as compared to CC alleles (32.43 µmol/L) and CT alleles (30.54 µmol/L). MTHFR A1298C, MS A2756G and CBS T833C genotypes did not showed significant association with higher Hcy levels. Thus, in Indian patients with thrombosis only MTHFR T677T genotype was observed to be significantly associated with hyperhomocysteinemia.