TRP64ARG beta 3-adrenergic receptor and obesity in Mexican Americans.
TRP64ARG beta 3-adrenergic receptor and obesity in Mexican Americans.
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TRP64ARG β 3-肾上腺素受体与墨西哥裔美国人的肥胖。
DOI：
10.1007/s004390050633
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发表时间：
1997
期刊：
影响因子：
5.3
通讯作者：
Shuldiner,AR
中科院分区：
文献类型：
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作者：
Silver,K;Mitchell,BD;Walston,J;Sorkin,JD;Stern,MP;Roth,J;Shuldiner,AR
β3肾上腺素能受体（β3AR）在内脏脂肪中表达，是静息代谢率、产热和脂解的调节剂。我们对61名无关的墨西哥裔美国人进行了β3AR基因变异（密码子64 TGGTrp→CGGArg; TRP 64 ARG）的基因分型。等位基因频率为0.13。TRP 64 ARG变异与非胰岛素依赖型糖尿病的早期发病年龄显著相关（41.3 ± 4.6岁vs 55.6 ± 2.6岁;P< 0.02），在非糖尿病患者中，口服葡萄糖耐量试验期间2小时胰岛素水平升高（810 ± 120 pmol/l vs 384 ± 6 pmol/l;P< 0.005）。非糖尿病受试者与变异等位基因往往有较高的体重指数（BMI），腰臀比，舒张压。研究组扩大到包括来自圣安东尼奥家庭糖尿病研究的31个家庭的421名相关受试者。使用测量的基因型分析方法来估计每个性状的基因型特异性平均值，与其他两种基因型相比，TRP 64 ARG变异纯合子的人具有显著更高的2小时胰岛素水平（P= 0.036）和更高的BMI趋势。我们没有发现这些性状的关联在TRP 64 ARG杂合子在较大的组。我们的结论是TRP 64 ARG β3AR变异是墨西哥裔美国人胰岛素抵抗综合征几个特征的易感基因。由于其影响是适度的，研究设计（例如，受试者选择、遗传背景和统计分析）可能影响哪些性状与该变体相关以及该效应是否在杂合子中可检测到。
The β3-adrenergic receptor (β3AR) is expressed in visceral fat and is a regulator of resting metabolic rate, thermogenesis, and lipolysis. We genotyped 61 unrelated Mexican Americans for a variant in the β3AR gene (codon 64 TGGTrp→CGGArg; TRP64ARG). The allele frequency was 0.13. The TRP64ARG variant was significantly associated with an earlier age of onset of non-insulin-dependent diabetes mellitus (41.3 ± 4.6 years vs 55.6 ± 2.6 years;P< 0.02) and in non-diabetics, with elevated 2-h insulin levels during an oral glucose tolerance test (810 ± 120 pmol/l vs 384 ± 6 pmol/l;P< 0.005). Non-diabetic subjects with the variant allele tended to have higher body mass indices (BMI), waist-to-hip ratios, and diastolic blood pressures. The study group was expanded to include 421 related subjects from 31 families in the San Antonio Family Diabetes Study. Using a measured genotype analysis approach to estimate genotype-specific means for each trait, those who were homozygous for the TRP64ARG variant had significantly higher 2-h insulin levels (P= 0.036) and trends towards higher BMI compared to the other two genotypes. We detected no associations of these traits in the TRP64ARG heterozygotes in the larger group. We conclude that the TRP64ARG β3AR variant is a susceptibility gene for several features of the insulin resistance syndrome in Mexican Americans. Since its effects are modest, study design (e.g., subject selection, genetic background, and statistical analyses) may influence which traits are associated with this variant and whether or not the effect is detectable in heterozygotes.