The impact of Trp64Arg mutation in the ß3-adrenergic receptor gene on haemodialysis patients

T. Yamauchi1,2, T. Kuno1, H. Takada2, K. Mishima2, Y. Nagura1, S. Takahashi3 and K. Kanmatsuse1

1 Second Department of Internal Medicine Nihon, University School of Medicine, Tokyo, Japan 2 Department of Hemodialysis, Toshima chuo Hospital, Tokyo, Japan 3 Nihon University, Graduate School of Business, Tokyo, Japan

Sir,

The ß3-adrenergic receptor (ß3-AR) is mainly expressed in adipose tissue and plays an important role in lipid metabolism and metabolic rate by mediating lipolysis and thermogenesis [1]. Recently a missense mutation in the ß3-AR gene (Trp64Arg) has been shown in various groups and reported to be associated with an early onset of NIDDM, an increased capacity to gain weight, visceral fat accumulation, and clinical features of insulin resistance syndrome [25]. It is well known that chronic HD patients have glucose intolerance and abnormalities in lipid metabolism [6,7]. However, there is no report about the mutation in the ß3-AR gene and its association with lipid and carbohydrate metabolism in HD patients. This is the first report to evaluate the impact of the above mutation in the ß3-AR gene on several parameters of HD patients, such as dialysis adequacy, body fat distribution, physical activity, lipid metabolism, and insulin resistance.

Seventy-five stable patients were studied after informed consent. Mutation in the ß3-AR gene was determined by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) analysis according to the method of Widen et al. [2], and classified according to genotype of ß3-AR gene. Per cent fat was measured by impedance analysis. Body fat distribution was determined by a computed tomography scanning technique according to the procedure of Tokugawa et al. [8]. Physical activity was assessed with their walking steps measured by pedometer. Fasting blood samples were drawn for several laboratory data included leptin [9]. The results are shown as mean±SEM in Table 1Go. Bonferroni t-test was performed after justification by one-way ANOVA.


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Table 1.
 
The allele frequency of the mutation (Arg) in HD patients was slightly, but not significantly, higher than that of the reference value in the general population in Japan (33 of 150 alleles (22.0%) vs. 40 of 248 (16.1%) respectively, P=0.09) [10]. No significant differences were found between the groups as to fat distribution or plasma leptin concentration. However, there was a tendency towards higher % fat, lower physical activity, lower PCR, higher insulin resistance, higher TG, and lower HDL-C among the mutation groups, especially Arg/Arg group.

Extremely low physical activities were found among the Arg/Arg group. This small group included one patient suffering from diabetic proliferative retinopathy and one suffering from rheumatoid arthritis. Since these complications would disturb their walking, the result may be underestimated.

In conclusion, our study suggests that the mutation in the ß3-AR gene affects fat accumulation and/or impairment of lipid and carbohydrate metabolism. Moreover, this genetic factor may have the potential to favour accelerated atherosclerosis; as proposed 20 years ago by Lindner et al., affecting multiple risk factors in HD population [11]. Particularly careful attention should be paid to the management of dialysis patients with this mutation.

References

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  11. Lindner A, Charra B, Sherrard DJ, Scribner BH. Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med1974; 290: 697–701[ISI][Medline]




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