Purpose The p15Ink4b gene exerts its influence as an inhibitor of
cyclin-dependent kinases and is frequently associated with hematological
malignancies. Inactivation of this gene through DNA methylation has been
found to be the most prevalent epigenetic alteration reported, with a high
frequency in all French-American-British subtypes of acute myeloid
leukemias, including acute promyelocytic leukemia (APL). In this study,we
investigated the prognostic significance of p15 gene promoter
hypermethylation and its expression in APL patients of Kashmir (North
India).Materials and Methods p15 gene promoter hypermethylation was conducted by methylation-specific
polymerase chain reaction, while its subsequent expression analysiswas
carried out by semi-quantitative reverse transcriptase polymerase chain
reaction (RT-PCR). Results Of the 37 patients, 16 (43.2%) were found to have methylated p15 genes. Of
these 16 cases, seven (43.8%) were methylated partially and nine (56.2%)
were found to have complete methylation. Moreover, nine of the 37 patients
(24.3%) who presented with leukocytosis at their baseline had complete p15
gene methylation as well (p < 0.05). Semiquantitative RT-PCR showed
a complete loss of p15 expression in nine patients with complete methylation
coupled with leukocytosis (p=0.031), while seven patients with
partial methylation showed decreased p15 expression. Six patients relapsed
during the maintenance phase of treatment and were found to have a
completely methylated p15 gene and no p15 mRNA.Conclusion Complete methylation and loss of p15 gene expression causes susceptibility to
relapse and decreased survival in APL patients. Thus, p15 promoter
hypermethylation is a prospective prognostic indicator and a reliable
clinical aid in assessment of patients with APL.
Background:Polycystic ovary syndrome (PCOS) is the most complex and common endocrine disorder of women in reproductive years. In addition to irregular menstrual cycles, chronic anovulation and hyperandrogenism, it has many metabolic manifestations such as obesity, hyperlipidemia, hyperinsulinemia, insulin resistance, dysglycemia, increased risk of cardiovascular disease or possibly endometrial cancer. Familial clustering of PCOS in consistence with the genetic susceptibility has been described.Materials and Methods:The present study assessed the clinical, biochemical and hormonal parameters including prevalence of metabolic syndrome by two different criteria in the first- degree relatives of patients with PCOS.Results:The average age of 37 index patients was 23 ± 3.6 years, with the mean age of menarche as 13.3 ± 1.2 years. The mean age and age of menarche in mothers (n = 22) was 48.8 ± 5.1 and 13 ± 1.3 years, respectively, whereas as it was 23.5 ± 4.7 and 13.3 ± 1.2 years in sisters (n = 22), respectively. Metabolic syndrome (MS) defined by International Diabetes Federation (IDF) criteria was present in 10 index patients, 1 brother, 4 sisters, 17 mothers and 15 fathers while as by Adult Treatment Panel III (ATP III) it was in 8 index patients, 5 sisters, 16 mothers and 11 fathers.Conclusion:The presence of MS or related metabolic derangements is high in the family members of women with PCOS.
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