%0 Journal Article
	%A Surajit Debnath and  Soma Addya
	%D 2012
	%J International Journal of Medical and Health Sciences
	%B World Academy of Science, Engineering and Technology
	%I Open Science Index 66, 2012
	%T Investigation of Genetic Epidemiology of
Metabolic Compromises in ß Thalassemia Minor
Mutation: Phenotypic Pleiotropy
	%U https://publications.waset.org/pdf/12173
	%V 66
	%X Human genome is not only the evolutionary
summation of all advantageous events, but also houses lesions of
deleterious foot prints. A single gene mutation sometimes may
express multiple consequences in numerous tissues and a linear
relationship of the genotype and the phenotype may often be obscure.
ß Thalassemia minor, a transfusion independent mild anaemia,
coupled with environment among other factors may articulate into
phenotypic pleotropy with Hypocholesterolemia, Vitamin D
deficiency, Tissue hypoxia, Hyper-parathyroidism and Psychological
alterations. Occurrence of Pancreatic insufficiency, resultant
steatorrhoea, Vitamin-D (25-OH) deficiency (13.86 ngm/ml) with
Hypocholesterolemia (85mg/dl) in a 30 years old male ß Thal-minor
patient (Hemoglobin 11mg/dl with Fetal Hemoglobin 2.10%, Hb A2
4.60% and Hb Adult 84.80% and altered Hemogram) with increased
Para thyroid hormone (62 pg/ml) & moderate Serum Ca+2
(9.5mg/ml) indicate towards a cascade of phenotypic pleotropy
where the ß Thalassemia mutation ,be it in the 5’ cap site of the
mRNA , differential splicing etc in heterozygous state is effecting
several metabolic pathways. Compensatory extramedulary
hematopoiesis may not coped up well with the stressful life style of
the young individual and increased erythropoietic stress with high
demand for cholesterol for RBC membrane synthesis may have
resulted in Hypocholesterolemia.Oxidative stress and tissue hypoxia
may have caused the pancreatic insufficiency, leading to Vitamin D
deficiency. This may in turn have caused the secondary
hyperparathyroidism to sustain serum Calcium level. Irritability and
stress intolerance of the patient was a cumulative effect of the vicious
cycle of metabolic compromises. From these findings we propose
that the metabolic deficiencies in the ß Thalassemia mutations may
be considered as the phenotypic display of the pleotropy to explain
the genetic epidemiology.
According to the recommendations from the NIH Workshop on
Gene-Environment Interplay in Common Complex Diseases: Forging
an Integrative Model, study design of observations should be
informed by gene-environment hypotheses and results of a study
(genetic diseases) should be published to inform future hypotheses.
Variety of approaches is needed to capture data on all possible
aspects, each of which is likely to contribute to the etiology of
disease. Speakers also agreed that there is a need for development of
new statistical methods and measurement tools to appraise
information that may be missed out by conventional method where
large sample size is needed to segregate considerable effect.
A meta analytic cohort study in future may bring about significant
insight on to the title comment.
	%P 265 - 269