An association between TRP64ARG polymorphism of the B3 adrenoreceptor gene and some metabolic disturbances

<p>Abstract</p> <p>Backgrounds</p> <p>B3 adrenoreceptors (ADRB3) are abundant in adipose tissue and play the role in its metabolism and lipolysis. Some variants of the ADRB3 gene may predispose subjects for the development obesity and metabolic abnormalities in the setting of modern sedentary lifestyle. ADRB3 gene polymorphism association with metabolic disturbances has never been studied before in the ethnic Kyrgyz population.</p> <p>Aim</p> <p>To study an association between Trp64Arg polymorphism of the ADRB3 and metabolic syndrome (MS) components in an ethnic Kyrgyz group.</p> <p>Materials and methods</p> <p>213 Ethnic Kyrgyz volunteers over the age of 30 were enrolled in the study. The assessment plan for each individual comprised of general physical and anthropometric exams as well as laboratory tests (glucose, lipid panel, insulin) and genotyping by Trp64Arg polymorphism of the ADRB3. MS diagnosis was consistent with modified ATP III criteria (2005). Logistic regression analysis was performed to test the potential independent association between Arg64 allele with obesity, abdominal obesity (AO) and arterial hypertension (AH).</p> <p>Results</p> <p>Trp64Arg polymorphism of the ADRB3 was assessed in 213 individuals (145 men, 68 women) aged 30-73 (mean age 50.7 ± 7.6). Arg64 allele frequency was 0.239; ADRB3 genotype distribution among participants was: Trp64 homozygotes 54.5%, Trp64Arg 43.2% and Arg64 homozygotes 2.3%. There was an association between Trp64Arg и Arg64Arg genotypes and higher BMI, WC and obesity frequency (p < 0.00009), AO (p < 0.01), type 2 diabetes mellitus (DM) (p < 0.005) and lower high density cholesterol (HDL-C) level (p < 0.03). The logistic regression analysis showed the correlation of the Arg64 allele with obesity (OR 3.159; 95% CI 1.789-5.577) and AO (OR 1.973; 95% CI 1.118-3.481). The association between Arg64 allele and AH lost its significance after adjustment for obesity.</p> <p>Conclusion</p> <p>Arg64 allele of the ADRB3 gene in the studied group has an association with MS components such as obesity, AO and decreased HDL-C level.</p

Genetic diversity and the emergence of ethnic groups in Central Asia

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Sex-Specific Genetic Structure and Social Organization in Central Asia: Insights from a Multi-Locus Study

In the last two decades, mitochondrial DNA (mtDNA) and the non-recombining portion of the Y chromosome (NRY) have been extensively used in order to measure the maternally and paternally inherited genetic structure of human populations, and to infer sex-specific demography and history. Most studies converge towards the notion that among populations, women are genetically less structured than men. This has been mainly explained by a higher migration rate of women, due to patrilocality, a tendency for men to stay in their birthplace while women move to their husband's house. Yet, since population differentiation depends upon the product of the effective number of individuals within each deme and the migration rate among demes, differences in male and female effective numbers and sex-biased dispersal have confounding effects on the comparison of genetic structure as measured by uniparentally inherited markers. In this study, we develop a new multi-locus approach to analyze jointly autosomal and X-linked markers in order to aid the understanding of sex-specific contributions to population differentiation. We show that in patrilineal herder groups of Central Asia, in contrast to bilineal agriculturalists, the effective number of women is higher than that of men. We interpret this result, which could not be obtained by the analysis of mtDNA and NRY alone, as the consequence of the social organization of patrilineal populations, in which genetically related men (but not women) tend to cluster together. This study suggests that differences in sex-specific migration rates may not be the only cause of contrasting male and female differentiation in humans, and that differences in effective numbers do matter

The zinc transporter ZIP12 regulates the pulmonary vascular response to chronic hypoxia

The typical response of the adult mammalian pulmonary circulation to a low oxygen environment is vasoconstriction and structural remodelling of pulmonary arterioles, leading to chronic elevation of pulmonary artery pressure (pulmonary hypertension) and right ventricular hypertrophy. Some mammals, however, exhibit genetic resistance to hypoxia-induced pulmonary hypertension1, 2, 3. We used a congenic breeding program and comparative genomics to exploit this variation in the rat and identified the gene Slc39a12 as a major regulator of hypoxia-induced pulmonary vascular remodelling. Slc39a12 encodes the zinc transporter ZIP12. Here we report that ZIP12 expression is increased in many cell types, including endothelial, smooth muscle and interstitial cells, in the remodelled pulmonary arterioles of rats, cows and humans susceptible to hypoxia-induced pulmonary hypertension. We show that ZIP12 expression in pulmonary vascular smooth muscle cells is hypoxia dependent and that targeted inhibition of ZIP12 inhibits the rise in intracellular labile zinc in hypoxia-exposed pulmonary vascular smooth muscle cells and their proliferation in culture. We demonstrate that genetic disruption of ZIP12 expression attenuates the development of pulmonary hypertension in rats housed in a hypoxic atmosphere. This new and unexpected insight into the fundamental role of a zinc transporter in mammalian pulmonary vascular homeostasis suggests a new drug target for the pharmacological management of pulmonary hypertension

Association between sleep apnoea and pulmonary hypertension in Kyrgyz highlanders

This case-control study evaluates a possible association between high altitude pulmonary hypertension (HAPH) and sleep apnoea in people living at high altitude.Ninety highlanders living at altitudes >2500 m without excessive erythrocytosis and with normal spirometry were studied at 3250 m (Aksay, Kyrgyzstan); 34 healthy lowlanders living below 800 m were studied at 760 m (Bishkek, Kyrgyzstan). Echocardiography, polysomnography and other outcomes were assessed. Thirty-six highlanders with elevated mean pulmonary artery pressure (mPAP) >30 mmHg (31-42 mmHg by echocardiography) were designated as HAPH+. Their data were compared to that of 54 healthy highlanders (HH, mPAP 13-28 mmHg) and 34 healthy lowlanders (LL, mPAP 8-24 mmHg).The HAPH+ group (median age 52 years (interquartile range 47-59) had a higher apnoea-hypopnoea index (AHI) of 33.8 events·h(-1) (26.9-54.6) and spent a greater percentage of the night-time with an oxygen saturation <90% (T<90; 78% (61-89)) than the HH group (median age 39 years (32-48), AHI 9.0 events·h(-1) (3.6-16), T<90 33% (10-69)) and the LL group (median age 40 years (30-47), AHI 4.3 events·h(-1) (1.4-12.6), T<90 0% (0-0)); p<0.007 for AHI and T<90, respectively, in HAPH+ versus others. In highlanders, multivariable regression analysis confirmed an independent association between mPAP and both AHI and T<90, when controlled for age, gender and body mass index.Pulmonary hypertension in highlanders is associated with sleep apnoea and hypoxaemia even when adjusted for age, gender and body mass index, suggesting pathophysiologic interactions between pulmonary haemodynamics and sleep apnoea

Percentage of significant tests in the (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) parameter space, for simulated data.

<p>We chose a range of 49 (<i>N</i>_f<i>m</i>_f/<i>N</i>_m<i>m</i>_m) ratios, varying from 0.0004 to 2401, and for each of these ratios we chose 29 sets of (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) values. By doing this, we obtained 1421 sets of (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) values, represented as white dots in the right-hand side panel B, covering the whole parameter space. For each set, we simulated 100 independent datasets using a coalescent-based algorithm, and taking the same number of individuals and the same number of loci for each genetic system as in the observed data. For each dataset, we calculated the <i>p</i>-value for a one-sided Wilcoxon sum rank test , and for each set of (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) values we calculated the percentage of significant <i>p</i>-values (at the <i>α</i> = 0.05 level). A. Surface plot of the proportion of significant <i>p</i>-values (at the <i>α</i> = 0.05 level), as a function of the female fraction of effective number and the female fraction of migration rate. B. Contour plot, for the same data. The dotted line, at which , represents the set of (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) values where the autosomal and X-linked <i>F</i>_ST's are equal. The theory predicts that we should only find in the upper-right triangle defined by the dotted line. Hence, the proportion of significant <i>p</i>-values for any set of (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) values in this upper right triangle gives an indication of the power of the method.</p

Diagram representing the relative values of expected genetic differentiation for autosomal markers and for X-linked markers .

<p>In the red upper right triangle, the <i>F</i>_ST estimates for autosomal markers are higher than for X-linked markers. In this case, <i>N</i>_f/<i>N</i> is necessarily larger than 0.5. In the blue region of the figure, the <i>F</i>_ST estimates for autosomal markers are lower than for X-linked markers. The white plain line, at which , represents the set of (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) values where the autosomal and X-linked <i>F</i>_ST estimates are equal. In this case , if <i>N</i>_f = <i>N</i>_m, then the lower effective size of X-linked markers (which would be three-quarters that of autosomal markers) can only be balanced by a complete female-bias in dispersal (<i>m</i>_f/<i>m</i> = 1). Conversely, if <i>m</i>_f = <i>m</i>_m, the large female fraction of effective numbers compensates exactly the low effective size of X-linked markers only for <i>N</i>_f = 7<i>N</i>_m. Last, if <i>m</i>_f = <i>m</i>_m/2, then the autosomal and X-linked <i>F</i>_ST estimates can only be equal as the number of males tends towards zero.</p