Association between fragile X premutation and premature ovarian failure: a case-control study and meta-analysis.

AIM: The aim of the present study was to investigate the association between FMR1 premutation and premature ovarian failure (POF) patients in Indian population, and a meta-analysis of published results was undertaken to clarify whether FMR1 premutation consistently contributed to the susceptibility. METHODS: A total of 289 POF samples and 360 control samples were included in the study. Repeat variation was checked using GeneScan technique. Results were analyzed with GeneMapper software. Meta-analysis was performed using the Open Meta-Analyst and STATA 12.0 software. The crude odds ratio with 95 % confidence interval (CI) was computed to assess the strength of the associations. RESULTS: The assayed case and control population showed 29 different CGG repeat sizes (alleles), ranging from 7 to 40. Within this population, we found that the CGG repeat length polymorphisms were within the normal range of 6-55 in both patients as well as control samples. Eleven case-control studies were included in the meta-analysis with a total of 1,313 POF cases and 3,132 control subjects. Our meta-analysis revealed that there was a significant difference in the incidence of FMR1 premutation between POF cases and control subjects with p value <0.001 (OR 5.41; 95 % CI 2.53, 11.61). CONCLUSIONS: We found no significant association between FMR1 CGG repeat premutation and POF in Indian population. However, the meta-analysis showed an increased risk of POF associated with a premutation, especially among populations from European descent. Further functional research should be performed to explain the inconsistent results in different ethnicities and POF susceptibility.

Gelatinase B (-1562C/T) polymorphism in tumor progression and invasion of breast cancer.

Matrix metalloproteinases (MMPs) play an important role in breast cancer tumor invasion and progression. MMP-9 is a member of the MMP family and is also known as Gelatinase B or type IV collagenases (92 kDa) and possesses proteolytic activity against type IV collagen, a major component of the basement membrane. Our study aims to examine the association of Gelatinase B (-1562C > T) promoter polymorphism with breast cancer invasion and progression. The study involves 200 breast cancer patients and age-matched 191 healthy controls. The SNP-1562C > T (rs3918242) in MMP-9 promoter region was examined by allele-specific polymerase chain reaction and gel electrophoresis. The genotypes were determined and compared between patients and controls, and the influence of the polymorphism on clinicopathological data was analyzed. The T allele of the -1562C > T MMP-9 polymorphism was detected more frequently in breast cancer patients than controls (p < 0.001). Our results suggest the clinical importance of MMP-9 gene polymorphism (-1562C > T) in breast cancer patients. The study may also help in identifying individuals at risk of developing breast cancer.

Endothelin-1 and endothelial nitric oxide polymorphisms in idiopathic pulmonary arterial hypertension.

Idiopathic Pulmonary arterial hypertension (IPAH) is a debilitating disease associated with very poor prognosis. The disease is characterised by endothelial dysfunction, smooth muscle proliferation and insitu thrombosis in the pulmonary artery, eventually leading to right ventricular failure. Two of the key endothelial mediators implicated in the pathogenesis of IPAH are endothelin-1 (EDN1) and nitric oxide (NO). EDN1 is a potent endogenous vasoconstrictor whereas NO is a vasodilator. In the present study screening of the EDN1 gene (EDN1) and NOS3 polymorphisms was taken up, to evaluate their association with IPAH. A significant association of EDN1 3A/4A polymorphism (+138 A; rs10478694) (OR-3.485; CI-1.254, 9.999; p=0.013) and EDN1 Lys198Asn polymorphism (G/T, rs5370) (OR-3.378, CI-1.104, 10.582; p=0.03) with IPAH was observed. Our results indicate that EDN1 polymorphisms in interaction with other genetic markers may play a significant role in individual's susceptibility to the disease and its clinical progression.

Risk factors for coronary heart disease in type II diabetes mellitus.

Cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. An attempt has been made to evaluate the risk factors for coronary heart disease in type II diabetics. In the present study the levels of fasting and postprandial plasma glucose, total cholesterol, low density lipoproteins, triglycerides were high and the levels of high density lipoproteins were low in the type II diabetics compared to controls. The markers of free radical induced injury i.e. malondialdehyde and nitrite/nitrate were high while total antioxidant status a marker for antioxidant protection against reactive oxygen species was low in diabetics compared to controls. The study therefore suggests the importance of assessing these markers of oxidative stress and antioxidant capacity along with the other routine investigations in diabetic patients for initiating antioxidant therapy in addition to primary and secondary preventive measures to mitigate the devastating consequences of diabetes leading to coronary heart disease.

Use of specific IgE to fractions of gynandropsis gynandra pollen inin vitro diagnostic test.

The study was aimed at presence of specific IgE antibody levelsinvitro to the identified antigen. Based on positive skin test with Gynandropsis gynandra and elevated levels of total IgE (>325 IU/ml) 104 patients were selected. Healthy, asymptomatic individuals (25) with low total IgE (<325 IU/ml) were included as controls. The mean OD values by ELISA for specific IgE were 0.67±0.21, 0.57±0.18 and 0.56±0.18 with whole pollen antigen, 46-37 kD fraction and 36-32 kD fraction, respectively. The specificity and sensitivity between skin test positivity with whole pollen antigen verses fraction with mol.wt 46-37 kD was 90% and 90% and for fraction with mol.wt 36-32 kD was found to be 81.1% and 89.4%. The clusters with molecular weights 46-37 kD and 36-32 kD may be useful inin vitro diagnostic test. Fractions within these clusters need to be identified for a higher specificity.