CDKAL1附近的2型糖尿病风险等位基因与中国汉族人群出生体重降低之间的正相关关系。
Positive Association Between Type 2 Diabetes Risk Alleles Near CDKAL1 and Reduced Birthweight in Chinese Han Individuals.
作者信息
Sun Xiao-Fang, Xiao Xin-Hua, Zhang Zhen-Xin, Liu Ying, Xu Tao, Zhu Xi-Lin, Zhang Yun, Wu Xiao-Pan, Li Wen-Hui, Zhang Hua-Bing, Yu Miao
机构信息
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Diabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
出版信息
Chin Med J (Engl). 2015 Jul 20;128(14):1873-8. doi: 10.4103/0366-6999.160489.
BACKGROUND
Fetal insulin hypothesis was proposed that the association between low birth weight and type 2 diabetes is principally genetically mediated. The aim of this study was to investigate whether common variants in genes CDKAL1, HHEX, ADCY5, SRR, PTPRD that predisposed to type 2 diabetes were also associated with reduced birthweight in Chinese Han population.
METHODS
Twelve single nucleotide polymorphisms (rs7756992/rs10946398 in CDKAL1, rs1111875 in HHEX, rs391300 in SRR, rs17584499 in PTPRD, rs1170806/rs9883204/rs4678017/rs9881942/rs7641344/rs6777397/rs6226243 in ADCY5) were genotyped in 1174 unrelated individuals born in Peking Union Medical College Hospital from 1921 to 1954 by TaqMan allelic discrimination assays, of which 645 had normal glucose tolerance, 181 had developed type 2 diabetes and 348 impaired glucose regulation. Associations of these 12 genetic variants with birthweight and glucose metabolism in later life were analyzed.
RESULTS
Birthweight was inversely associated with CDKAL1-rs10946398 (β = -41 g [95% confidence interval [CI]: -80, -3], P = 0.034), common variants both associated with increased risk of impaired glucose metabolism and decreased insulin secretion index later in life. After adjusting for sex, gestational weeks, parity and maternal age, the risk allele of CDKAL1-rs7756992 was associated with reduced birthweight (β = -36 g [95% CI: -72, -0.2], P = 0.048). The risk allele in SRR showed a trend toward a reduction of birthweight (P = 0.085).
CONCLUSIONS
This study identified the association between type 2 diabetes risk variants in CDKAL1 and birthweight in Chinese Han individuals, and the carrier of risk allele within SRR had the trend of reduced birthweight. This demonstrates that there is a clear overlap between the genetics of type 2 diabetes and fetal growth, which proposes that lower birth weight and type 2 diabetes may be two phenotypes of one genotype.
背景
胎儿胰岛素假说提出低出生体重与2型糖尿病之间的关联主要是由基因介导的。本研究的目的是调查在中国汉族人群中，易患2型糖尿病的基因CDKAL1、HHEX、ADCY5、SRR、PTPRD中的常见变异是否也与出生体重降低有关。
方法
采用TaqMan等位基因鉴别分析法，对1921年至1954年在北京协和医院出生的1174名无亲缘关系个体中的12个单核苷酸多态性（CDKAL1中的rs7756992/rs10946398、HHEX中的rs1111875、SRR中的rs391300、PTPRD中的rs17584499、ADCY5中的rs1170806/rs9883204/rs4678017/rs9881942/rs7641344/rs6777397/rs6226243）进行基因分型，其中645人糖耐量正常，181人已患2型糖尿病，348人糖耐量受损。分析这12个基因变异与出生体重及晚年糖代谢的关联。
结果
出生体重与CDKAL1-rs10946398呈负相关（β=-41g[95%置信区间[CI]：-80，-3]，P=0.034），这些常见变异均与晚年糖代谢受损风险增加及胰岛素分泌指数降低有关。在调整性别、孕周、产次和母亲年龄后，CDKAL1-rs7756992的风险等位基因与出生体重降低有关（β=-36g[95%CI：-72，-0.2]，P=0.048）。SRR中的风险等位基因有出生体重降低的趋势（P=0.085）。
结论
本研究确定了中国汉族个体中CDKAL1基因的2型糖尿病风险变异与出生体重之间的关联，且SRR中风险等位基因的携带者有出生体重降低的趋势。这表明2型糖尿病遗传学与胎儿生长之间存在明显重叠，提示低出生体重和2型糖尿病可能是同一基因型的两种表型。
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