Objective. Human urate transporter 1 (hURAT1) is a member of the organic anion transporter family (SLC22A12) that mainly regulates tubular urate reabsorption. Loss-of-function mutations result in idiopathic hypouricemia. The present case-control study was designed to analyze whether hURAT1 might also be a candidate gene for hyperuricemia with primary reduced renal urate excretion.Methods. DNA samples from 389 individuals with reduced fractional excretion of uric acid (FEUA) (<6.5%) and from 263 controls (FEUA >6.5%) were sequenced. Genotype frequencies between groups were compared by Cochran-Armitage trend test.Results. Significantly different genotype distributions could be demonstrated for the ؊788 T>A (promoter; P ؍ 0.014), the C258T (exon 1; P ؍ 0.006), and the C426T (exon 2; P ؍ 0.0002) polymorphisms, but not for the T1309C (exon 8) and the ؉18 C>T (intron 9) polymorphisms. The strongest association with reduced FEUA was observed for the C426T polymorphism, with odds ratios (ORs) of 1.59 and 2.54 (P ؍ 0.0002) for the CT and TT genotypes, respectively. Adjusted values for FEUA in the C426T genotype, were significantly reduced decreasing to 7.3%, 6.7%, and 6.3% in individuals with the CC, CT, and TT genotypes, respectively (P ؍ 0.004). Haplotypes were constructed from the ؊788 T>A, C258T, and C426T polymorphisms. Individuals carrying at least 1 ACT haplotype (n ؍ 349) had a significantly higher risk for reduced FEUA than individuals without any ACT haplotype (n ؍ 303) (OR 1.39, P ؍ 0.041).Conclusion. These results indicate that polymorphisms in the N-terminus of the hURAT1 gene were significantly associated with reduced renal uric acid excretion. The main regulating factor seems to be located close to the C426T polymorphism or is in strong linkage disequilibrium.In Germany, as in most Western countries, the prevalence of hyperuricemia is ϳ30% in men and 3% in women (1). Of these individuals, ϳ10% develop gout. The familial nature of hyperuricemia and gout has long been recognized. Among family members of patients with gout, the prevalence of asymptomatic hyperuricemia ranges from 25% to 27% (2,3). In a study of twins, Emmerson et al (4) observed that monozygotic twins had more similar values of urate clearance and fractional excretion of uric acid (FEUA) than did dizygotic twins. The heritability of the renal urate clearance was estimated as ϳ60%, whereas the heritability of the fractional urate excretion was found to be 87% (4). In Ͼ90% of patients with primary gout, reduced renal uric acid clearance causes hyperuricemia.Glomerular filtration and bidirectional urate transport, including both tubular secretion and reabsorption, are the essential physiologic processes in renal handling of uric acid (5). Under normal conditions, uric acid is freely filtered at the kidney glomerulus and almost completely reabsorbed from urine in the proximal tubule. According to the "four-component model" of urate excretion (6), net urate excretion is determined by tubular urate secretion and postsecretory urate ...
Long-haul flights of 8 hours and longer double the risk for isolated calf muscle venous thrombosis. This translates into an increased risk for deep venous thrombosis as well. In our study, flight-associated thrombosis occurred exclusively in passengers with well-established risk factors for venous thrombosis.
The risk of venous thromboembolism associated with long-haul flights is the subject of controversy. In a prospective, controlled study, we examined 160 passengers before and after return from a long-haul flight and 160 age-matched and sex-matched, non-travelling volunteers using venous compression ultrasound. Deep vein thrombosis was not observed in either group. Isolated calf muscle vein thrombosis (ICMVT) was present in 4/160 (2.5%) flight passengers and in 1/160 (0.6%) controls. All subjects with ICMVT were clinically asymptomatic, and ICMVT was located in the soleal muscle veins in all four subjects. Three of the four passengers with ICMVT had other risk factors for thrombosis.
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