Biomedical subjects

Jim L Rupert

Publications and source records attributed to Jim L Rupert.

4 recordsLinked to original sources

PubMed2006

Evidence for a genetic basis for altitude-related illness.

Altitude-related illnesses are a family of interrelated pulmonary, cerebral, hematological, and cardiovascular medical conditions associated with the diminished oxygen availability at moderate to high altitudes. The acute forms of these debilitating and potentially fatal conditions, which include acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE), often develop in incompletely acclimatized lowlanders shortly after ascent, whereas, the chronic conditions, such as chronic mountain sickness (CMS) and high altitude pulmonary hypertension (HAPH), usually afflict native or long-term highlanders and may reflect a loss of adaptation. Anecdotal reports of particularly susceptible people or families are frequently cited as evidence that certain individuals have an innate susceptibility (or resistance) to developing these conditions and, in recent decades, there have been a number of studies designed to characterize the physiology of individuals predisposed to these conditions, as well as to identify the specific genetic variants that contribute to this predisposition. This paper reviews the epidemiological evidence for a genetic component to the various forms of altitude-related illness, such as innate susceptibility, familial clustering, and patterns of population susceptibility, as well as the molecular evidence for specific genetic risk factors. While the evidence supports some role for genetic background in the etiology of altitude-related illness, limitations in individual studies and a general lack of corroborating research limit the conclusions that can be drawn about the extent of this contribution and the specific genes or pathways involved. The paper closes with suggestions for future work that could support and expand on previous studies, as well as provide new insights.

Acute Disease↗

PubMed2006

No association between variants in the ACE and angiotensin II receptor 1 genes and acute mountain sickness in Nepalese pilgrims to the Janai Purnima Festival at 4380 m.

Koehle, Michael S., Pei Wang, Jordan A. Guenette, and Jim L. Rupert. No association between variants in the ACE and angiotensin II receptor 1 genes and acute mountain sickness in Nepalese pilgrims to the Janai Purnima Festival at 4380 m. High Alt. Med. Biol. 7:281-289, 2006.--Acute mountain sickness (AMS) causes significant morbidity among visitors to altitude. The primary contributors to developing AMS are altitude and rate of ascent; however, the substantial variation in susceptibility between individuals has led a number of investigators to propose that there may be genetic predilection to the disease. The ACE I/D polymorphism has been shown to predict performance among elite mountaineers. This study compares genotype and allele frequencies at the ACE I/D locus, two other loci in the ACE gene, and one locus in the angiotensin-2 receptor gene between individuals who did, or did not, express signs of AMS while attending a high altitude religious festival in Nepal (4380 m). Subjects (80 males, 23 females) were recruited and genotyped. All subjects were Nepalese. Forty-four of the subjects had been diagnosed with AMS by physicians at a high altitude health camp; the rest were free from altitude illness. All subjects were genotyped at polymorphic loci in the genes encoding angiotensin converting enzyme (ACE) and angiotensin II receptor type 1 gene (AGTR1). The polymorphisms examined were two single nucleotide polymorphisms (SNPs) in ACE (ACE(A-240T), dbSNP rs4291; and ACE(A2350G), dbSNP rs4343), the intronic Alu insertion in ACE (ACE I/D), and the SNP ATR(A1166C), (dbSNP rs17231380) in AGTR1d. All polymorphisms in ACE were found to be in linkage disequilibrium. No significant associations were found between AMS incidence and any of the alleles, suggesting that variants at these loci do not contribute to susceptibility to AMS in this population.

Acute Disease↗

PubMed2003

Fine tuning the HIF-1 'global' O2 sensor for hypobaric hypoxia in Andean high-altitude natives.

Included in the acute response of lowlanders exposed to reduced oxygen availability is an elevated red blood cell count due to increased erythropoietin (Epo) synthesis. According to current thinking, hypoxia is "sensed" by hydroxylases that permit Hypoxia Inducible Factor 1alpha (HIF-1alpha) to complex with HIF-1beta to form a transcriptional activator (HIF-1) that drives expression of hypoxia-sensitive genes (such as EPO) under hypoxic conditions. In altitude-adapted Andean natives, the Epo hypoxic response may be blunted; however, our data indicate that the DNA sequences of the genes encoding Epo (including the 3' regulatory region) and HIF-1alpha appear to be conserved. Hence, adaptive changes in the Andean hypoxic response are not a consequence of changes in the primary sequence of these proteins or of known transcriptional regulatory domains of EPO. These results suggest that the altered erthropoietic response in Andean natives reflects adaptations in hypoxia sensing, rather than hypoxia response, mechanisms.

Altitude↗

PubMed2003

The search for genotypes that underlie human performance phenotypes.

For a species spread throughout the world, humans are remarkably invariant; yet there has always been more interest in the slight differences between individuals than in the great commonality. This is especially true in athletic endeavours, where nearly immeasurable differences in performance can separate the winner from the rest of the competitors. There is little doubt that performance is influenced by environment, as the effects of diet and training on athletic ability have long been known, if not completely understood; however, the contribution of an individual's genetic make-up is less clear. The dominance of particular nationalities, ethnic groups, or families in various sporting events is often perceived as evidence that heritage (biological or cultural), plays a role in the development of athletic skills. Further complicating the issue are the interactions between genetic background and environment, as both of these fundamental arbiters of development rarely act independently. Despite the complexity of the problem, numerous researchers have attempted to elucidate the effects of genetic background on physical performance and, more recently, to identify the specific genetic variants that contribute to performance. This article reviews some of these studies with a focus on the methodologies employed.

Adaptation, Physiological↗