High-altitude adaptation: Role of genetic and epigenetic factors.

After the completion of the Human Genome Project in 2003, the field of genetics has witnessed massive progress that spanned research in high-altitude biology also. Especially the decade of 2010s witnessed the most of it and revealed various genetic signatures of high-altitude adaptation in Tibetans, Andeans and Ethiopians. High-altitude area, with its extreme environment, harbors a tremendous potential for gene-environment interaction, an aspect that could be explored by epigenetic studies. There are only four original articles till now which explore the epigenetic aspect of high-altitude adaptation or acclimatization. However, there is no comprehensive review to provide complete information on the genetic and epigenetic aspects of high-altitude adaptations. Hence, we have prepared this mini-review to summarize the genetic and epigenetic studies that have correlated the high-altitude adaptation or acclimatization, until recently.

Heterogeneity in Hematological Parameters of High and Low Altitude Tibetan Populations.

INTRODUCTION: High altitude hypoxia is believed to be experienced at elevations of more than 2500 meters above sea level. Several studies have shed light on the biochemical aspects of high altitude acclimatization, where participants were sojourners to the high altitude from low altitude areas. However, information regarding the difference between the high altitude adapted Tibetans living at high altitude and their counterparts who reside at low altitude are lacking. To understand this, we have measured various hematological parameters in the Tibetan populations, who are residing in both high and low altitudes in India. METHODS: A total of 168 individuals (79 from high altitude (≥4500 meters) and 89 from low altitude (~850 meters) were recruited for this study. Hematological parameters such as red blood cells (RBC) count, hematocrit (HCT), hemoglobin concentration (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were measured from the individuals from high and low altitudes. Serum erythropoietin (EPO) was measured by ELISA. Statistical analyses were performed to compare data from both of the altitudes. Gender-wise comparison of data was reported. Correlation analysis was performed within relevant parameters. RESULTS: Highly significant differences (p <0.0001) between high and low altitude Tibetans were detected in RBC count, HCT, Hb, MCHC in both males and females and in MCV in females. In the case of MCHC, however, age and BMI were potential confounders. Nominally significant differences (p <0.05) were detected in MCV and MCH within males. No significant difference in serum EPO level was found between altitude groups, in any gender. No significant correlation was found between serum EPO with Hb as well as serum EPO with HCT. DISCUSSION: Our study explores significantly lower RBC count, HCT, Hb, MCH, MCHC and higher MCV in long-term Tibetan residents living at low altitude compared to their high altitude counterparts, which is likely due to the outcome of hematological adaptation to a relatively hyperoxic environment in low altitude areas.

Variations in macrophage migration inhibitory factor gene are not associated with visceral leishmaniasis in India.

BACKGROUND: The host genetic factors play important role in determining the outcome of visceral leishmaniasis (VL). Macrophage migration inhibitory factor (MIF) is an important host cytokine, which is a key regulator of innate immune system. Genetic variants in MIF gene have been found to be associated with several inflammatory and infectious diseases. Role of MIF is well documented in leishmaniasis diseases, including Indian visceral leishmaniasis, where elevated level of serum MIF has been associated with VL phenotypes. However, there was no genetic study to correlate MIF variants in VL, therefore, we aimed to study the possible association of three reported MIF gene variants -794 CATT, -173G > C and non-coding RNA gene LOC284889 in Indian VL phenotype. METHODS: Study subjects comprised of 214 VL patients along with ethnically and demographically matched 220 controls from VL endemic regions of Bihar state in India. RESULTS: We found no significant difference between cases and controls in allelic, genotypic and haplotype frequency of the markers analysed [-794 CATT repeats (χ2=0.86; p=0.35; OR=0.85; 95% CI=0.61-1.19); -173 G>C polymorphism (χ2=1.11; p=0.29; OR=0.83; 95% CI=0.59-1.16); and LOC284889 (χ2=0.78; p=0.37; OR=0.86; 95% CI=0.61-1.20)]. CONCLUSION: Since we did not find any significant differences between case and control groups, we conclude that sequencing of complete MIF gene and extensive study on innate and adaptive immunity genes may help in identifying genetic variations that are associated with VL susceptibility/resistance among Indians.