Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins
Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins
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DOI：
10.1038/ijo.2008.68
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发表时间：
2008-08-01
影响因子：
4.9
通讯作者：
Zeegers, M. P.
中科院分区：
文献类型：
--
作者：
Souren, N. Y.;Paulussen, A. D.;Zeegers, M. P.
目的：出生时小于胎龄的儿童在成年后患2型糖尿病的风险增加。调节食物摄入和能量消耗的饱腹感信号瘦素可能是一个可能的分子联系，因为脐带瘦素水平与出生体重呈正相关。在本研究中，我们检测了瘦素基因中常见的单核苷酸多态性（SNP）是否与瘦素基因的表达有关。（LEP; 19 G>A）基因及其受体（LEPR; Q223 R和K109 R）与双胞胎中2型糖尿病的出生体重和成人代谢危险因素相关。设计：从东弗兰德斯前瞻性双胞胎调查中招募的396例单卵双胞胎和232例双卵双胞胎（286例男性和342例女性，平均年龄25岁）进行SNP基因分型。结果：LEPR K109 R基因多态性与出生体重相关（KK、KR和RR（95%可信区间，CI）：2511（2465 ~ 2557）、2575（2516-2635）和2726（2606-2845）克; P-加性= 0.001）。此外，LEPR Q223 R SNP显示与出生时体重显著相关（QQ、QR和RR（95%CI）：2492（2431-2554）、2545（2495-2595）和2655（2571-2740）克; P-加性= 0.003）。此外，观察到LEPR K109 R和Q223 R SNP对出生体重的相互作用（P = 0.014）。与19 A纯合子相比，LEP 19 G>A SNP的G等位基因携带者具有更高的高密度脂蛋白（HDL）胆固醇水平（GX vs AA（95% CI）：1.62（1.58-1.66）vs 1.49（1.40-1.58）mmol l（-1）; P-隐性= 0.013）。这项研究表明，瘦素可能作为一个促进生长的信号在胎儿发育，并提出了一个可能的作用，LEPR在解释出生体重和代谢性疾病的发展在成年期之间的负相关关系。此外，这些结果表明LEP 19 G>A SNP影响HDL胆固醇水平。
Objective: Children born small for gestational age are at increased risk of developing type 2 diabetes in adulthood. The satiety signal leptin that regulates food intake and energy expenditure might be a possible molecular link, as umbilical cord leptin levels are positively correlated with birth weight. In the present study, we examined whether common single nucleotide polymorphisms (SNPs) in the leptin (LEP; 19G>A) gene and its receptor (LEPR; Q223R and K109R) are associated with birth weight and adult metabolic risk factors for type 2 diabetes in twins.Design: SNPs were genotyped in 396 monozygotic and 232 dizygotic twins (286 men and 342 women, mean age 25 years) recruited from the East Flanders Prospective Twin Survey. Data were analysed using linear mixed models.Results: The LEPR K109R SNP was associated with birth weight (KK, KR and RR (95% confidence interval, CI): 2511 (2465 2557), 2575 (2516-2635) and 2726 (2606-2845) gram; P-additive = 0.001). Also the LEPR Q223R SNP showed a significant association with weight at birth (QQ, QR and RR (95% CI): 2492 (2431-2554), 2545 (2495-2595) and 2655 (2571-2740) gram; P-additive = 0.003). Furthermore, an interaction between the LEPR K109R and the Q223R SNP on birth weight was observed (P = 0.014). G allele carriers of the LEP 19G>A SNP had higher high-density lipoprotein (HDL) cholesterol levels compared to 19A homozygotes (GX vs AA (95% CI): 1.62 (1.58-1.66) vs 1.49 (1.40-1.58) mmol l(-1); P-recessive = 0.013).Conclusions: This study indicates that leptin may act as a growth-promoting signal during fetal development, and suggests a possible role for the LEPR in explaining the inverse relationship between birth weight and the development of metabolic diseases in adulthood. Additionally, these results suggest that the LEP 19G>A SNP affect HDL cholesterol levels.