Doney Alex S F, Fischer Bettina, Cecil Joanne E, Cohen Patricia T W, Boyle Douglas I, Leese Graham, Morris Andrew D, Palmer Colin N A
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, United Kingdom.
BMC Genet. 2003 Jun 28;4:11. doi: 10.1186/1471-2156-4-11.
The ARE insertion/deletion polymorphism of PPP1R3A has been associated with variation in glycaemic parameters and prevalence of diabetes. We have investigated its role in age of diagnosis, body weight and glycaemic control in 1,950 individuals with type 2 diabetes in Tayside, Scotland, and compared the ARE2 allele frequencies with 1,014 local schoolchildren.
Men homozygous for the rarer allele (ARE2) were younger at diagnosis than ARE1 homozygotes (p = 0.008). Conversely, women ARE2 homozygotes were diagnosed later than ARE1 homozygotes (p = 0.036). Thus, men possessing the rarer (ARE2) allele were diagnosed with type 2 diabetes earlier than women (p < 0.000001). In contrast, there was no difference in age of diagnosis by gender in those individuals carrying only the common ARE1 variant. Furthermore, although there was no difference in the frequency between the children and the type 2 diabetic population overall, marked differences in allele frequencies were noted by gender and age-of diagnosis. The ARE2 allele frequency in early diagnosed males (diagnosed earlier than the first quartile of the overall ages at diagnosis) was higher than that found in both later diagnosed males and healthy children (p = 0.021 and p = 0.03 respectively). By contrast, the frequency in early diagnosed females was significantly lower than later diagnosed females and that found in children (p = 0.021 and p = 0.037). Comparison of the male to female ratios at different ages-diagnosed confirms a known phenomenon that men are much more prone to early type 2 diabetes than women. When this feature was examined by the common ARE 1/1 genotype we found that the male to female ratio remained at unity with all ages of diagnosis, however, carriers of the ARE2 variant displayed a marked preponderance of early male diagnosis (p = 0.003).
The ARE2 allele of PPP1R3A is associated with a male preponderance to early diagnosed type 2 diabetes. Susceptibility to type 2 diabetes in later life is not modulated by the ARE2 allele in either sex.
PPP1R3A基因的ARE插入/缺失多态性与血糖参数变化及糖尿病患病率相关。我们在苏格兰泰赛德地区的1950例2型糖尿病患者中研究了其在诊断年龄、体重和血糖控制方面的作用，并将ARE2等位基因频率与1014名当地学童进行了比较。
携带较罕见等位基因（ARE2）的男性纯合子在诊断时比ARE1纯合子年龄更小（p = 0.008）。相反，女性ARE2纯合子的诊断时间比ARE1纯合子更晚（p = 0.036）。因此，携带较罕见（ARE2）等位基因的男性比女性更早被诊断出2型糖尿病（p < 0.000001）。相比之下，仅携带常见ARE1变体的个体在诊断年龄上没有性别差异。此外，尽管儿童与2型糖尿病总体人群之间的频率没有差异，但按性别和诊断年龄观察到等位基因频率存在显著差异。早期诊断的男性（诊断时间早于总体诊断年龄的第一个四分位数）中的ARE2等位基因频率高于晚期诊断的男性和健康儿童（分别为p = 0.021和p = 0.03）。相比之下，早期诊断的女性中的频率显著低于晚期诊断的女性和儿童中的频率（分别为p = 0.021和p = 0.037）。不同诊断年龄的男女比例比较证实了一个已知现象，即男性比女性更容易患早期2型糖尿病。当通过常见的ARE 1/1基因型检查这一特征时，我们发现各诊断年龄的男女比例均保持一致，然而，ARE2变体携带者中早期男性诊断明显占优势（p = 0.003）。
PPP1R3A基因的ARE2等位基因与男性在早期诊断2型糖尿病方面占优势有关。晚年2型糖尿病易感性在两性中均不受ARE2等位基因的调节。
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