Lys418Asn Polymorphism of the α2-Adrenoceptor Gene Relates to Serum Uric Acid Levels But Not to Insulin Sensitivity

Abstract

Abstract-Hyperuricemia is associated with cardiovascular risk. The present study examines the association between serum uric acid (UA) elevation and the ␣2-, ␤2-, and ␤3-adrenoceptor polymorphisms. In 219 nonobese, normotensive, normouricemic (serum UA Ͻ6.5 mg/dL at entry) men, serum UA, plasma norepinephrine (NE), the homeostasis model assessment of insulin resistance (HOMA-IR), body mass index, total body fat mass, the ␣2A(Lys418Asn)-, ␤2(Arg16Gly, Gln27Glu)-, and ␤3(Trp64Arg)-adrenoceptor polymorphisms were measured annually over 5 years.Hyperuricemia was defined as a serum UA level of Նmeanϩ1 SD of 5.0 mg/dL in the participants. At entry, there were 36 subjects who had hyperuricemia and 183 who had normal UA levels. A significant UA elevation for 5 years was defined as an increase in Ն10% in UA levels. There were 82 subjects who had significant UA elevations. The subjects who had hyperuricemia at entry in addition to the subjects who had significant UA elevations over the 5-year period carried a significantly higher frequency of the Asn418 allele of Lys418Asn. Additionally, subjects carrying the Asn418 allele had higher UA and plasma NE and greater elevations in UA over the study period, but HOMA-IR was similar. Insulin resistance at entry and during the study was associated with Arg16Gly polymorphisms but not with Lys418Asn polymorphisms. In conclusion, the Asn418 allele of Lys418Asn is associated with either established hyperuricemia or the progressive elevation of UA over time. This polymorphism was not associated with insulin resistance in nonobese, normotensive individuals. Although hyperuricemia is of known relevance to insulin resistance, it appears to have different genetic determinants from insulin resistance in terms of adrenoceptor polymorphisms. Key Words: uric acid Ⅲ polymorphism Ⅲ insulin resistance M any large epidemiological studies have identified a strong association between increased serum uric acid (UA) and cardiovascular risk such as increased hypertension or coronary heart disease in the general population. [1][2][3][4][5][6][7] We also reported that serum UA level predicts future blood pressure (BP) elevation and weight gain in a longitudinal study. 8 The metabolic syndrome and insulin resistance are clustered by the additional associations of hyperuricemia, obesity, hypertriglyceridemia, glucose intolerance, and hypertension. Thus, hyperuricemia is thought of as an inherent component of the metabolic syndrome. UA also has been proposed as a marker of insulin resistance; 9 -11 however, others claim that a serum UA is more a risk factor for cardiovascular disease rather than insulin resistance. 12 Insulin resistance is recognized to have some genetic components of which polymorphisms of the ␤2-and ␤3-adrenoceptor system play an important role. [13][14][15][16][17] Similar to UA, total body fat mass or stored fat in the abdominal area (abdominal obesity) is closely related to insulin resistance and ␣2A-adrenoceptor polymorphism. 18 The present study examined the relationship between alte...

High Plasma Norepinephrine Levels Associated with .BETA.2-Adrenoceptor Polymorphisms Predict Future Renal Damage in Nonobese Normotensive Individuals

“…Genotyping was performed by the TaqMan assay as previously described (16,19,21,22). Two polymorphisms in the β2-adrenergic receptors (arginine/glycine substitution, Arg16Gly; glutamine/glutamate substitution, Gln27Glu) of the β2-adrenoceptor genes (16,17) were evaluated.…”

Gender, Body Mass Index, and PPARγ Polymorphism Are Good Indicators in Hyperuricemia Prediction for Han Chinese

“…The prevalence of obesity/overweight in Taiwan has been increasing alarmingly (Page et al, 2004;Ho and Tsai, 2007); therefore, an understanding of the fundamental mechanism of hyperuricemia becomes critical to prevent hyperuricemia in Han Chinese in Taiwan. Previous studies indicated that hyperuricemia was associated with a long list of candidate genes such as solute carrier family 2, member 9 (SLC2A9) (Rule et al, 2011), solute carrier family 22, member 12 (SLC22A12) ( Jang et al, 2008), and solute carrier family 17, member 3 (SLC17A3) (Polasek et al, 2010). Additional candidates include the genes encoding ATP-binding cassette, sub-family G, member 2 (ABCG2) (Yamagishi et al, 2010), klotho (KL) (Shimoyama et al, 2009), guanine nucleotide binding protein, beta polypeptide 3 (GNB3) (Suwazono et al, 2006), methylenetetrahydrofolate reductase (MTHFR) (Zuo et al, 2000), nitric oxide synthase 3 (NOS3) (Wang et al, 2007), adrenoceptor beta 2 (ADRB2) (Masuo et al, 2005), and adrenoceptor beta 3 (ADRB3) (Wang et al, 2002). However, considerable heterogeneity on the putative hyperuricemia loci was observed among different ethnic groups.…”

Effects of Antidepressants, but not Psychopathology, on Cardiac Sympathetic Control: A Longitudinal Study

“…Increased activity of the sympathetic nervous system (SNS) may have an important role in the increased risk for cardiovascular and metabolic disease in patients with depressive and anxiety disorders (Glassman, 2008;Penninx et al, 2001;Eaker et al, 2005;Nicholson et al, 2006;Esler et al, 2006;Flaa et al, 2008a, b;Masuo et al, 2005Masuo et al, , 2010. Various studies reported increased sympathetic activity in depressed and anxious subjects compared with healthy controls, measured by different indices like spillover of norepinephrine (NE) and epinephrine (EPI), skin conductance responses, QT interval variability (QTvi), or the pre-ejection period (PEP) (Light et al, 1998;Esler et al, 1982;Guinjoan et al, 1995;Gold et al, 2005;Koschke et al, 2009;Barton et al, 2007).…”