Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
PLoS One. 2012;7(11):e48785. doi: 10.1371/journal.pone.0048785. Epub 2012 Nov 13.
Pubertal timing is under strong genetic control and its early onset associates with several adverse health outcomes in adulthood, including obesity, type 2 diabetes and cardiovascular disease. Recent data indicate strong association between pubertal timing and genetic variants near LIN28B, but it is currently unknown whether the gene contributes to the association between puberty and adult disease.
To elucidate the putative genetic link between early puberty and adult disease risk, we examined the association of two genetic variants near LIN28B with adult body size and metabolic profiles in randomly ascertained adult Finnish males and females.
Two single nucleotide polymorphisms (SNPs), rs7759938, the lead SNP previously associated with pubertal timing and height, and rs314279, previously also associated with menarcheal age but only partially correlated with rs7759938 (r(2) = 0.30), were genotyped in 26,636 study subjects participating in the Finnish population survey FINRISK. Marker associations with adult height, weight, body mass index (BMI), hip and waist circumference, blood glucose, serum insulin and lipid/lipoprotein levels were determined by linear regression analyses.
Both rs7759938 and rs314279 associated with adult height in both sexes (p = 2×10(-6) and p = 0.001). Furthermore, rs314279 associated with increased weight in females (p = 0.001). Conditioned analyses including both SNPs in the regression model verified that rs314279 independently associates with adult female weight, BMI and hip circumference (p<0.005). Neither SNP associated with glucose, lipid, or lipoprotein levels.
Genetic variants near the puberty-associated gene LIN28B associate with adult weight and body shape in females, suggesting that the gene may tag molecular pathways influencing adult adiposity-related traits.
青春期开始的时间受强烈的遗传控制，其早期开始与成年后多种健康结果相关，包括肥胖、2 型糖尿病和心血管疾病。最近的数据表明，青春期开始的时间与 LIN28B 附近的遗传变异之间存在强烈的关联，但目前尚不清楚该基因是否与青春期和成年疾病之间的关联有关。
为了阐明青春期早期与成年疾病风险之间潜在的遗传联系，我们检查了 LIN28B 附近的两个遗传变异与随机确定的成年芬兰男性和女性的成人身体大小和代谢特征的关联。
两个单核苷酸多态性（SNP），rs7759938，之前与青春期开始和身高相关的主要 SNP，以及 rs314279，之前也与初潮年龄相关，但仅与 rs7759938 部分相关（r(2) = 0.30），在参加芬兰人群调查 FINRISK 的 26636 名研究对象中进行了基因分型。通过线性回归分析确定标记与成人身高、体重、体重指数（BMI）、臀围和腰围、血糖、血清胰岛素和血脂/脂蛋白水平的关联。
rs7759938 和 rs314279 在两性中均与成人身高相关（p = 2×10(-6)和 p = 0.001）。此外，rs314279 与女性体重增加相关（p = 0.001）。在回归模型中包含两个 SNP 的条件分析验证了 rs314279 独立与成年女性体重、BMI 和臀围相关（p<0.005）。两个 SNP 均与葡萄糖、脂质或脂蛋白水平无关。
与青春期相关基因 LIN28B 附近的遗传变异与女性成年体重和体型相关，表明该基因可能标记影响成年肥胖相关特征的分子途径。
