Lillian Gleiberman

A BDNF Coding Variant Is Associated with the NEO Personality Inventory Domain Neuroticism, a Risk Factor for Depression

, but with traits, such as personality factors, that are themselves associated with risk for the disorder (Lander and Schork, 1994; Stolten-berg and Burmeister, 2000). Often such traits have a higher heritability than the disease status (Almasy and Blangero, 2001). Neuroticism, as measured by the NEO personality inventory (NEO-PI) (Costa and McCrae, 1997), a psycho-metrically sound and widely used instrument, is one such trait. High scorers on the Neuroticism domain are char-acterized by frequent experience of “negative emotional-ity” such as anxiety, low mood, and hostility. Converging lines of evidence point to brain-derived neurotrophic fac-tor (BDNF) as a factor in the pathophysiology of depres-sion. To explore the possibility that variation in the BDNF gene is, in part, responsible for the population variation in Neuroticism, we studied a community sample of 441 sub-jects, genotyping a G→A single-nucleotide polymorphism (SNP) responsible for a valine→methionine substitution in the prodomain of BDNF. The less common, nonconserved Met allele was associated with significantly lower mean Neuroticism scores (

Serotonin Transporter and GABA(A) Alpha 6 Receptor Variants Are Associated with Neuroticism

BACKGROUND A tendency to experience negative affect, as measured by the neuroticism component of the Neuroticism, Extraversion, and Openness Personality Inventory (NEO-PI), is a trait marker for major depression. Epidemiologic studies indicate a strong genetic component, but to date few specific genetic variants have been definitively implicated. A serotonin transporter promoter polymorphism (5-HTTLPR) has been extensively studied in neuroticism and several psychiatric disorders, with inconclusive results. A GABA(A) receptor alpha6 subunit variant (Pro385Ser) has been associated with alcohol-related traits but has not been studied in neuroticism or depression. METHODS A total of 384 subjects who completed the NEO-PI were genotyped at 5-HTTLPR and Pro385Ser. Associations between polymorphisms and both alcohol use and personality domains were tested. RESULTS The 5-HTTLPR short allele (p =.008) and Pro385Ser Pro allele (p =.003) are associated with higher neuroticism scores. The 5-HTTLPR long allele (p =.006), but not Pro385Ser, is also associated with an increased presence of alcohol use. In addition, there is a nonsignificant suggestion of an interaction: the effect of 5-HTTLPR on neuroticism might be dependent on the Pro385Ser genotype. CONCLUSIONS These findings support a role for the serotonin transporter and GABA(A) alpha6 subunit in depression-related traits.

Glutathione and morbidity in a community-based sample of elderly

This study examined the association of blood glutathione level, a potential marker of physiological/functional aging, with a number of biomedical/psychological traits in a subgroup (N = 33) of a representative sample of community-based elderly. Higher glutathione levels were associated with fewer number of illnesses (p < 0.05), higher levels of self-rated health (p < 0.01), lower cholesterol (p < 0.05), lower body mass index, and lower blood pressures. Subjects with diagnoses of arthritis, diabetes, or heart disease (as assessed by physicians) had at least marginally significant lower glutathione levels than those who were disease free. Glutathione, together with age and a measure of suppressed anger, accounted for 39% of the variance of an index of morbidity. Glutathione, by itself, accounted for 24% of the variance. To our knowledge, this is the first evidence of an association of higher glutathione levels with higher levels of physical health in a sample of community-based elderly. Further studies in large samples are needed to investigate glutathione as a potential overall health risk factor for morbidity among the elderly.

Erythrocyte Sodium-Lithium Countertransport and Blood Pressure. A Genome-Wide Linkage Study

Abstract—Increased activity of erythrocyte sodium-lithium countertransport is associated with essential hypertension. Sodium-lithium countertransport is highly heritable, but no single gene product mediating the exchange or explaining the association of increased sodium-lithium countertransport activity and hypertension has been identified. We performed a linkage study by using erythrocyte sodium-lithium countertransport as a quantitative phenotype and genome-wide markers at an average resolution of ≈10 cM to identify quantitative trait loci explaining sodium-lithium countertransport activity. A peak LOD score of 2.83 was detected on chromosome 15q at D15S642, a marker previously shown to be linked to blood pressure. Several genes mapped to this region are possible candidates for factors affecting erythrocyte sodium-lithium countertransport and/or blood pressure. Further studies confirming the presence of a quantitative trait locus in this region and evaluating these candidate genes may help explain the association of elevated sodium-lithium countertransport and hypertension.

Whites Excrete a Water Load More Rapidly Than Blacks

A recent report demonstrated a racial difference in response to furosemide compatible with increased ion reabsorption in the thick ascending limb of the loop of Henle in blacks. Urinary dilution is another function of the loop-diuretic–sensitive Na,K,2Cl cotransporter in the thick ascending limb, and racial differences in urinary diluting capacity have not been reported previously. We assessed diluting segment (cortical thick ascending limb and distal convoluted tubule) function in black and white normotensives in 2 studies using a water-loading approach. In both studies, we found that whites excreted a water load more rapidly than blacks. In the first study, the final free water clearance rates (mean±SD) were 7.3±4.7 mL/min in whites (n=17, 7 females and 10 males) and 3.8±3.6 mL/min in blacks (n=14, 9 females and 5 males; P<0.03). In the second study, final free water clearance rates were 8.3±2.6 mL/min in whites (n=17, 8 females and 9 males) and 6.4±1.8 mL/min in blacks (n=11, 8 females and 3 males; P<0.01). We found no evidence of a racial difference in renal proximal tubular fluid reabsorption as assessed by renal endogenous lithium clearance or in plasma vasopressin level that could explain the difference in free water excretion. We conclude that our observations are most consistent with a lower capacity of ion reabsorption in the renal diluting segment in blacks. Slower excretion of an acute water load may have been an advantage during natural selection of humans living in arid, hot climates.

A gender blind relationship of lean Body mass and blood pressure in the tecumseh study

BACKGROUND Body size correlates positively with blood pressure (BP) but there is controversy about the roles of obesity versus muscularity in this relationship. METHODS We examined the BP relationship with overweight, lean body mass (LBM), and muscle performance in 231 adolescents (17.25 +/- 3.07 years, 123 males). The skinfold thickness (SKINT) was used to measure overweight, as this was a growing population. RESULTS Maximal foot torque, a measure of muscle strength, correlated strongly (r = 0.51, P < .001) to LBM attesting to the validity of the calculated LBM. Anthropometric measurements were available also in 944 adults (29.9 +/- 5.5 years, 461 men). Correlations of LBM to systolic (adolescents r = 0.52, adults r = 0.19, both P < .001) and diastolic (adolescents r = 0.47, adults r = 0.20, both P < .001) BP were highly significant. SKINT also correlated significantly to systolic and diastolic BP in adolescents and in adults, respectively. In both genders and populations an increasing SKINT was associated with a similar increase in BP, but this effect was superimposed on an average 10 mm Hg between-gender BP difference. The LBM in both groups and genders related to the BP in an identical fashion; the men were on the high and the women on the low end of the same BP/LBM correlation line. Thus, the amount of LBM erased categoric BP differences between the genders. CONCLUSIONS The gender-related BP differences appear to reflect the inherent gender differences in muscle bulk.

Sodium, blood pressure, and ethnicity: What have we learned?

An enormous amount of research has yielded significant knowledge about ethnic differences in sodium homeostasis and blood pressure regulation. Consistent findings such as greater sodium‐sensitivity, lower potassium excretion and high higher serum sodium levels in African Americans need further exploration to define more precise physiological mechanisms. The genetic alleles associated with sodium homeostasis in relation to blood pressure have accounted for only a small proportion of the variance in blood pressure. Several allelic variants differ in frequency among ethnic groups and heat‐adapted genetic variants have a high prevalence in low latitudes and hot, wet climates which lends support to the “sodium retention” hypothesis. The blood pressure disparities between African Americans and whites may, in part, be due to different allelic frequencies of genes associated with sodium homeostasis. However, with advances in genomics, environmental factors tend to be neglected in research. Better measures of environmental stress have recently been developed by anthropologists and should be included in research designs by investigators in other disciplines. Public health efforts should encourage food producers to reduce sodium content of its products, and physicians should encourage patients to reduce consumption of high sodium packaged and fast foods. Am. J. Hum. Biol., 2009.

Urinary dopamine excretion and renal responses to fenoldopam infusion in blacks and whites.

Dopamine is an endogenous natriuretic amine that contributes to the maintenance of sodium homeostasis. Deficiencies in the renal production of dopamine and the action of dopamine on renal tubular receptors have been observed in human hypertension and may contribute to salt sensitivity of blood pressure. Ethnic differences in the sodium‐to‐dopamine relationship may contribute to the higher prevalence of salt sensitivity in blacks. The authors assessed dopaminergic activity in two studies. In the first, daytime and nighttime excretion of sodium and dopamine were compared in 11 black and 17 white normotensive patients. No racial difference in the rate of sodium or dopamine excretion during either period was observed. In the second study, a graded infusion of the dopamine‐1 receptor agonist, fenoldopam, was performed in 14 black and 17 white normotensive patients. There was no racial difference in the natriuretic responses. Previously described lower rates of renal free water clearance and potassium excretion in blacks compared with whites were maintained during fenoldopam infusion, suggesting that dopamine is not a mediator of those differences. The authors conclude that there are no race‐related differences in dopamine excretion or activity in normotensive patients.

Anger Types: Heritability and Relation to Blood Pressure, Body Mass Index, and Left Ventricular Mass

The relationship between anger and cardiovascular morbidity has not been investigated among Mexican Americans. This exploratory study examined the heritability of anger types and their relationship to cardiovascular variables in samples of unrelated and related Mexican Americans residing near Chicago, Illinois. All of the anger variables of the Spielberger Anger Expression Scale (in, out, control, total expression) had significant heritabilities. Using the total sample of related individuals, higher female anger‐out scores were associated with greater left ventricular mass after correction for height to the 2.7 power (LVM/HT 2.7 ), systolic blood pressure, and diastolic blood pressure. Females had positive, significant associations for body mass index with LVM/HT 2.7 , systolic blood pressure, and diastolic blood pressure; among males, these variables were similarly but less strongly related. Anger (coraje in Spanish) is discussed in the context of folk medicine as a risk factor for cardiovascular morbidity.

Blood pressure and blood group markers: association with the MN locus.

The relationship of blood pressure levels to 12 blood, salivary and serum protein polymorphisms is reported for a sample of 4000+ adult Caucasians from Tecumseh, Michigan. Males with the MN phenotype had significantly higher unadjusted systolic and diastolic blood pressures than those who were homozygous MM or NN. When blood pressure was adjusted for age and weight, males who were Duffy (a-) had higher diastolic pressures than those who were Duffy (a+), and females who were Kidd (b-) had higher diastolic pressures than females who were Kidd (b+). A review of studies reporting on MN- blood pressure associations indicates that six of the eight presented significant findings. These findings, and others from the literature, present evidence that the MN locus (and possibly the Jk locus) actively participates in controlling the response to environmental/dietary stimuli affecting differences in blood pressure. We suggest that the MN blood group be investigated further, particularly vis-à-vis physiological parameters known to be related to blood pressure.