Univariate Genetic Analysis of Oxygen Transport Regulation in Children: The Medical College of Virginia Twin Study

Abstract

ABSTRACT. We investigated the relative contributions of genetic, individual environmental, and shared environmental effects on 2,3-diphosphoglycerate (DPG) regulation in preadolescent children. In a population of 165 early pubescent boy and girl twin pairs (11.4 y old), of whom 63 were passive smokers, we asked: 1 ) Are there differences in the control of DPG levels between early pubertal boys and girls? 2) If present, are these differences influenced by exposure to passive cigarette smoke? Non-passive-smoking boys and girls had similar DPG levels. With exposure to passive smoke, DPG levels increased in boys ( p = 0.02) but not in girls. Analysis of variance on DPG demonstrated a parental smoking effect ( p = 0.008) and suggested an interactive effect between parental smoking and sex of the child (p = 0.08). Univariate genetic analyses suggested that genes operated at different magnitudes in boys (9%) and girls (39%) in explaining a significant portion of the variance in DPG. The magnitude of shared environmental influences was greater in boys (62%) than in girls (34%), whereas individual environmental effects were similar in boys (29%) and girls (26%). Early pubertal boys differ from girls in their regulation of DPG. Environmental stressors such as passive cigarette smoke may elicit different responses in males and females, even at an early age. The use of path analysis may provide important insights into the mechanisms and interactions of genetic and environmental effects that underly the childhood antecedents of atherosclerotic heart disease. (Pediatr Res 33: [645][646][647][648] 1993) Abbreviations DPG, 2,3-diphosphoglycerate Systemic oxygen transport is accomplished using many integrated, self-regulated organ systems. Essential components of this system include pulmonary gas exchange, blood flow, Hb concentration, and Hb affinity for oxygen (1). Organic phosphates within the red cell decrease the oxygen affinity of Hb. The most important quantitatively is DPG. The mechanism of the DPG effect on oxygen affinity involves binding of DPG to the two beta chains in the central cavity of deoxy Hb, forcing a conformational shift that drives oxygen off. Oxyhemoglobin (as well as carboxyhemoglobin) binds DPG poorly because of a stereochemically smaller central cavity created by changes in the quarternary structure of Hb with oxygenation (2). An increase in red-cell DPG compensates for an impairment in oxygen supply to tissue and is proportional to the increase in deoxyhemoglobin concentration.Considerable variation in DPG levels, Hb levels, and oxygen affinity occurs in the normal population. A negative correlation has been observed between Hb levels and the levels of DPG in normal people (3, 4). Measurement of red-cell DPG levels has been used as a "functional biopsy" of the adequacy of tissue oxygenation (5). Whereas the correlation between DPG and Hb level may not be causal, feedback mechanisms appear to regulate them in tandem. Therefore, DPG may function as a monitor for environmental influences on systemic ...

Επίδραση Της Διακοπής Καπνίσματος Σε Δείκτες Φλεγμονής

“…2,3 -DPG ( 2,3-diphosphoglycerate), που αποτελεί σημαντικό ρυθμιστικό παράγοντα της ικανότητας της αιμοσφαιρίνης για σύνδεση με το οξυγόνο. Η συγκέντρωση του 2,3-DPG είναι αυξημένη στους καπνιστές σε μια προσπάθεια του οργανισμού να αντιρροπίσει το υποξαιμικό περιβάλλον που δημιουργείται από το μονοξείδιο του άνθρακα [68]. Εντούτοις πιο πρόσφατα δεδομένα δείχνουν ότι ο ρόλος του μονοξειδίου του άνθρακα στην διαδικασία της αθηρωμάτωσης είναι αμφιλεγόμενος και ίσως δεν αποτελεί αιτία αθηροσκλήρωσης και δημιουργίας θρόμβου [69].…”