Biomedical subjects

R Pesich

Publications and source records attributed to R Pesich.

4 recordsLinked to original sources

PubMed2001

Genetic variation in aldosterone synthase predicts plasma glucose levels.

The mineralocorticoid hormone, aldosterone, is known to play a role in sodium homeostasis. We serendipitously found, however, highly significant association between single-nucleotide polymorphisms in the aldosterone synthase gene and plasma glucose levels in a large population of Chinese and Japanese origin. Two polymorphisms--one in the putative promoter (T-344C) and another resulting in a lysine/arginine substitution at amino acid 173, which are in complete linkage disequilibrium in this population--were associated with fasting plasma glucose levels (P = 0.000017) and those 60 (P = 0.017) and 120 (P = 0.0019) min after an oral glucose challenge. A C/T variant in intron 1, between these polymorphisms, was not associated with glucose levels. Arg-173 and -344C homozygotes were most likely to be diabetic [odds ratio 2.51; 95% confidence interval (C.I.) 1.39-3.92; P = 0.0015] and have impaired fasting glucose levels (odds ratio 3.53; 95% C.I. 2.02-5.5; P = 0.0000036). These results suggest a new role for aldosterone in glucose homeostasis.

Adult↗

PubMed2001

Genetic variation in the human urea transporter-2 is associated with variation in blood pressure.

The kidney, by regulating the volume of fluid in the body, plays a key role in regulating blood pressure (BP). The kidney uses primarily sodium and, to a lesser extent, urea to maintain the appropriate volume of fluid. Genetic variation in proteins that determine sodium reabsorption and excretion is known to significantly influence BP. However, the influence of genetic variation in urea transporters on BP has not been examined. We determined therefore whether nucleotide variation in the kidney-specific human urea transporter, HUT2, is associated with variation in BP. After determining the genomic structure of the coding sequence, seven single nucleotide polymorphisms (SNPs) were identified. Two of the SNPs result in Val/Ile and Ala/Thr amino acid substitutions at positions 227 and 357 in the HUT2 open reading frame, respectively. Another SNP is silent and four others are in introns or the 3' untranslated region. Over 1000 hypertensive and low-normotensive individuals of Chinese origin were typed for five of these SNPs using a high-throughput genotyping method. The Ile227 and Ala357 alleles were associated with low diastolic BP in men but not women, with odds ratios 2.1 [95% confidence interval (CI) 1.5-2.7, P < 0.001] and 1.5 (95% CI 1.2-1.8, P < 0.001), respectively. There was a similar trend for systolic BP, and odds ratios for the Ile227 and Ala357 alleles were 1.7 (95% CI 1.2-2.3, P = 0.002) and 1.3 (95% CI 1.1-1.6, P = 0.007), respectively, in men.

Blood Pressure↗

PubMed2001

The glycine allele of a glycine/arginine polymorphism in the beta2-adrenergic receptor gene is associated with essential hypertension in a population of Chinese origin.

BACKGROUND: Several studies implicate polymorphisms in the human beta-adrenergic receptor gene (ADRB2) in the susceptibility to hypertension. We sought to replicate these results in a population of Chinese origin primarily from Taiwan and the San Francisco Bay area. METHODS: We genotyped >800 hypertensive subjects and individuals with low-normal blood pressure that were derived largely from the same families as the hypertensive patients for three polymorphisms in the ADRB2 gene: a C/T transition at position 47 (C-47T) in the 5' leader cistron; another C/T transition that results in a glycine/ arginine substitution at codon 16 (Gly16Arg), and a G/C transversion that causes a glutamate/glutamine substitution at codon 27 (Glu27Gln). RESULTS: The Gly16Arg was significantly associated with hypertension (P < .03). Under a dominant model, for hypertension the relative risk for the Gly/Gly and Gly/Arg genotypes versus the Arg/Arg genotype was 1.35 (95% confidence limits [CL] 1.08, 1.70); for low-normal blood pressure the relative risk was 0.79 (95% CL 0.66, 0.94). This polymorphism explained approximately 1% of the variance in systolic and diastolic blood pressures in our study population. There was no evidence of association between the C-47T and Glu27Gln polymorphisms and hypertension in this population. CONCLUSIONS: The Glyl6 allele in the beta2-adrenergic receptor gene is a susceptibility allele for essential hypertension in a population of Chinese origin.

Arginine↗

PubMed2001

High-throughput genotyping with single nucleotide polymorphisms.

To make large-scale association studies a reality, automated high-throughput methods for genotyping with single-nucleotide polymorphisms (SNPs) are needed. We describe PCR conditions that permit the use of the TaqMan or 5' nuclease allelic discrimination assay for typing large numbers of individuals with any SNP and computational methods that allow genotypes to be assigned automatically. To demonstrate the utility of these methods, we typed >1600 individuals for a G-to-T transversion that results in a glutamate-to-aspartate substitution at position 298 in the endothelial nitric oxide synthase gene, and a G/C polymorphism (newly identified in our laboratory) in intron 8 of the 11-beta hydroxylase gene. The genotyping method is accurate-we estimate an error rate of fewer than 1 in 2000 genotypes, rapid-with five 96-well PCR machines, one fluorescent reader, and no automated pipetting, over one thousand genotypes can be generated by one person in one day, and flexible-a new SNP can be tested for association in less than one week. Indeed, large-scale genotyping has been accomplished for 23 other SNPs in 13 different genes using this method. In addition, we identified three "pseudo-SNPs" (WIAF1161, WIAF2566, and WIAF335) that are probably a result of duplication.

Alleles↗