Variants in CXADR and F2RL1 are associated with blood pressure and obesity in African-Americans in regions identified through admixture mapping

OBJECTIVE:: Genetic variants in 296 genes in regions identified through admixture mapping of hypertension, BMI, and lipids were assessed for association with hypertension, blood pressure (BP), BMI, and high-density lipoprotein cholesterol (HDL-C). METHODS:: This study identified coding SNPs identified from HapMap2 data that were located in genes on chromosomes 5, 6, 8, and 21, wherein ancestry association evidence for hypertension, BMI, or HDL-C was identified in previous admixture mapping studies. Genotyping was performed in 1733 unrelated African-Americans from the National Heart, Lung and Blood Institute's Family Blood Pressure Project, and gene-based association analyses were conducted for hypertension, SBP, DBP, BMI, and HDL-C. A gene score based on the number of minor alleles of each SNP in a gene was created and used for gene-based regression analyses, adjusting for age, age, sex, local marker ancestry, and BMI, as applicable. An individual's African ancestry estimated from 2507 ancestry-informative markers was also adjusted for to eliminate any confounding due to population stratification. RESULTS:: CXADR (rs437470) on chromosome 21 was associated with SBP and DBP with or without adjusting for local ancestry (P?相似文献   

Genetic variation in APOL1 and MYH9 genes is associated with chronic kidney disease among Nigerians

Purpose

A region of chromosome 22 which includes APOL1 and MYH9 genes was recently identified as a risk locus for non-diabetic forms of kidney disease, including idiopathic and HIV-associated focal segmental glomerular sclerosis and kidney disease clinically attributed to hypertension among African Americans. The purposes of the current study were, therefore, to examine the frequency of these variants and to determine whether they are associated with chronic kidney disease (CKD) among native Africans.

Methods

To investigate the possible evidence of association between variants in these genes and non-diabetic CKD among West Africans, we performed a case/control analysis in a sample of 166 Nigerians without history of European admixture. Our study included a total of 9 variants on APOL1 (n = 4) and MYH9 (n = 5) genes.

Results

We observed significantly strong associations with previously reported APOL1 variants rs73885319 and rs60910145, and their two-allele “G1” haplotype (P < 0.005). We did not observe significant evidence of association between non-diabetic CKD and any of the MYH9 variants or haplotypes after accounting for multiple testing in our sample.

Conclusions

In conclusion, APOL1 risk variants are associated with non-diabetic forms of CKD among Nigerians of Yoruba ethnicity. Further information on APOL1/MYH9 variants may lead to screening programs, which could lead to earlier detection and interventions for non-diabetic kidney disease.     

Involvement of Nax sodium channel in peripheral nerve regeneration via lactate signaling

Na_x, a sodium concentration‐sensitive sodium channel, is expressed in non‐myelinating Schwann cells of the adult peripheral nervous system, but the pathophysiological role remains unclear. We found that functional recovery of the hind paw responses from the sciatic nerve transection was delayed in Na_x knockout ( ) mice. Histological analyses showed a decrease in the number of regenerated myelinated axons in sciatic nerves. The delay in the recovery in mice was improved by lactate and inhibited by a monocarboxylate transporter inhibitor. In vitro experiments using cultured Schwann cells showed that lactate release was enhanced by endothelin (ET)‐1 and blocked by an ET receptor type B antagonist. Here, it is conceivable that Na_x was activated by ET‐1. The amount of lactate release by ET‐1 was lower in mice than in wild‐type mice. These results indicated that Na_x is functionally coupled to ET for lactate release via ET receptor type B and is involved in peripheral nerve regeneration.     

Pharmacology and thermosensitivity of the dartos muscle isolated from rat scrotum

1 The dartos is a thin sheet of smooth muscle closely associated with the skin of the scrotum. Although known to play an important role in scrotal thermoregulation, there has been no detailed study into the pharmacology, or thermosensitivity, of the dartos from any species. Here, we investigate these two parameters in the isolated dartos muscle from rat. 2 Field stimulation of the rat dartos caused contractions that were abolished by tetrodotoxin, phentolamine and guanethidine, but unaffected by atropine or L-N(G)-nitroarginine. Exogenous noradrenaline also produced contractions blocked by both phentolamine and prazosin. In muscles with raised tone and negated sympathetic function, field stimulation failed to elicit relaxation. The dartos muscle did not contract in response to carbachol, nicotine, histamine, 5-hydroxytryptamine (all up to 100 micro M) or substance P (up to 1 micro M). 3 Contractile responses to field stimulation and noradrenaline were much greater at 30 degrees C compared with 40 degrees C; indeed, contractions to 1 micro M noradrenaline at 30 degrees C were relaxed by around 80% on heating to 40 degrees C. Similar heat-induced relaxations were observed during contractions to both U46619 (100 nM) and high K (70 mM). 4 In contrast, contractile responses to the myosin phosphatase inhibitor calyculin-A (1 micro M), either in the presence or absence of external calcium, were resistant to relaxation by heating. In calcium-free medium at 30 degrees C, U46619 continued to produce contractions that were again relaxed by 80% on heating to 40 degrees C. However, in the presence of calyculin-A, this heat-induced relaxation was greatly reduced. 5 Thus, the rat dartos muscle receives a functional sympathetic innervation and contracts to noradrenaline via alpha-adrenoceptors. There is no functional inhibitory innervation. Experiments with calyculin-A suggest that myosin phosphatase is a major contributor to the marked thermosensitivity of the dartos muscle.     

Heritability of blood pressure in Nigerian families

OBJECTIVES: There are few studies of familial aggregation of blood pressure in African populations. This study was undertaken to provide estimates of heritability for four blood pressure phenotypes: systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure. METHODS : A population-based sample of 528 pedigrees or extended families, comprising 1825 measured individuals, was studied in a poor urban community in Ibadan, Nigeria. RESULTS : The mean SBP was 121.7 (SD 22.6) mmHg for men and 120.7 (SD 26.8) mmHg for women, while the mean DBP was 74.6 (SD 14.1) mmHg for men and 75.5 (SD 15.2) mm Hg for women. The study sample was lean [mean body mass index (BMI) approximately 21 kg/m2]. Maximum-likelihood heritability estimates were obtained under a polygenic model with simultaneous estimation of household effects using a variance components method, as implemented in the SOLAR software package. Heritability estimates of the traits were 34% for SBP, 29% for DBP, 36% for MAP and 13% for pulse pressure. Household effects were statistically significant for DBP (7.1%) and MAP (4.5%). Measured covariates (age, sex and BMI) accounted for 25, 24, 26 and 16% of the total variance, respectively, for SBP, DBP, MAP and pulse pressure. CONCLUSIONS : These figures suggest that, similar to that reported in other populations, blood pressure is a heritable trait. Studies similar to this are needed to describe the familial aggregation of other complex traits in sub-Saharan African populations and to serve as a prelude to the identification of susceptibility genes involved in the pathophysiology of common complex diseases, including blood pressure and hypertension.