Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Clin Chim Acta. 2012 Aug 16;413(15-16):1222-5. doi: 10.1016/j.cca.2012.03.025. Epub 2012 Apr 4.
The FTO gene plays an important role in the determination of body weight and BMI and it has been suspected of being associated with all-cause mortality, cardiovascular disease, cancer and end stage renal disease, but the causal mechanism of these effects is still unknown. One of the possibilities is the potential association with telomere length. Telomeres are repetitive DNA-sequences located at the ends of eukaryotic chromosomes' length of which is reduced in all somatic cells during ageing. Out of the 908 females (3PMFs study), in 783 females both FTO 1st intron tagging polymorphism (G>T, rs17817449) and the relative telomere length were successfully analysed. The relative telomere length was calculated as the ratio of telomere repeats to single-copy gene copies. The frequencies of the FTO genotypes were similar to other populations (GG=18.3%, GT=49.1% and TT=32.6%). We have detected, that the relative telomere length was significantly shorter (P<0.02, P<0.01 after adjustment for age, BMI, waist and subcutaneous fat), in carriers of at least one FTO risky (G) allele (0.85±0.39) in comparison to the carriers of the protective TT genotype (0.93±0.48). We have demonstrated that the FTO variant could be associated with the relative telomere length. Whether this represents a causality of association between the FTO variant and the non-communicable diseases needs to be further analysed.
FTO 基因在体重和 BMI 的决定中起着重要作用，它被怀疑与全因死亡率、心血管疾病、癌症和终末期肾病有关，但这些影响的因果机制尚不清楚。其中一种可能性是与端粒长度的潜在关联。端粒是位于真核染色体末端的重复 DNA 序列，在衰老过程中，所有体细胞的端粒长度都会缩短。在 908 名女性（3PMFs 研究）中，有 783 名女性成功分析了 FTO 第一内含子标记多态性（G>T，rs17817449）和相对端粒长度。相对端粒长度的计算方法是端粒重复与单拷贝基因拷贝的比值。FTO 基因型的频率与其他人群相似（GG=18.3%，GT=49.1%和 TT=32.6%）。我们发现，至少携带一个 FTO 风险（G）等位基因（0.85±0.39）的携带者的相对端粒长度明显更短（P<0.02，调整年龄、BMI、腰围和皮下脂肪后 P<0.01）与保护性 TT 基因型（0.93±0.48）的携带者相比。我们已经证明，FTO 变体可能与相对端粒长度有关。这种 FTO 变体与非传染性疾病之间的关联是否代表因果关系，需要进一步分析。
