Cohen Robert M, Snieder Harold, Lindsell Christopher J, Beyan Huriya, Hawa Mohammed I, Blinko Stuart, Edwards Raymond, Spector Timothy D, Leslie R David G
Division of Endocrinology, Medicine, General Clinical Research Center, Emergency Medicine, University of Cincinnati, Ohio, USA.
Diabetes Care. 2006 Aug;29(8):1739-43. doi: 10.2337/dc06-0286.
HbA(1c) (A1C) is substantially determined by genetic factors not shared in common with glucose. Fractions of the variance in A1C, the glycation gap (GG; previously called the glycosylation gap) and the hemoglobin glycosylation index, correlate with diabetes complications. We therefore tested whether GG (measured A1C - A1C predicted from glycated serum proteins [GSPs]) was genetically determined and whether it accounted for the heritability of A1C.
We conducted a classic twin study on A1C and GSP collected in 40 and 46 pairs of monozygotic and dizygotic healthy female twins, respectively. The predicted A1C was based on the regression line between A1C and GSP in a separate population spanning the pathophysiologic range.
GG was more strongly correlated between monozygotic (r = 0.65) than dizygotic (r = 0.48) twins, adjusted for age and BMI. The best-fitting quantitative genetic model adjusted for age and BMI showed that 69% of population variance in GG is heritable, while the remaining 31% is due to unique environmental influences. In contrast, GSP was similarly correlated between monozygotic (r = 0.55) and dizygotic (r = 0.49) twins, hence not genetically determined. GG was strongly correlated to A1C (r = 0.48), attributable mostly to genetic factors. About one-third of the heritability of A1C is shared with GG; the remainder is specific to A1C.
Heritability of the GG accounts for about one-third of the heritability of A1C. By implication, there are gene(s) that preferentially affect erythrocyte lifespan or glucose and/or nonenzymatic glycation or deglycation in the intracellular, rather than extracellular, compartment.
糖化血红蛋白A1C（HbA(1c)，A1C）很大程度上由与葡萄糖不共有的遗传因素决定。A1C的方差分数、糖化间隙（GG；以前称为糖基化间隙）和血红蛋白糖基化指数与糖尿病并发症相关。因此，我们测试了GG（测量的A1C减去根据糖化血清蛋白[GSPs]预测的A1C）是否由遗传决定，以及它是否解释了A1C的遗传力。
我们分别对40对同卵健康女性双胞胎和46对异卵健康女性双胞胎收集的A1C和GSP进行了经典双胞胎研究。预测的A1C基于跨越病理生理范围的另一个人群中A1C与GSP之间的回归线。
在根据年龄和体重指数进行调整后，同卵双胞胎（r = 0.65）之间的GG相关性比异卵双胞胎（r = 0.48）更强。根据年龄和体重指数进行调整的最佳拟合数量遗传模型表明，GG中69%的人群方差是可遗传的，而其余31%归因于独特的环境影响。相比之下，同卵双胞胎（r = 0.55）和异卵双胞胎（r = 0.49）之间的GSP相关性相似，因此不是由遗传决定的。GG与A1C高度相关（r = 0.48），主要归因于遗传因素。A1C遗传力的约三分之一与GG共享；其余部分是A1C特有的。
GG的遗传力约占A1C遗传力的三分之一。这意味着存在一些基因，它们优先影响红细胞寿命或细胞内而非细胞外区室中的葡萄糖和/或非酶糖基化或去糖基化。
