Positive Association Between Type 2 Diabetes Risk Alleles Near CDKAL1 and Reduced Birthweight in Chinese Han Individuals

被引：17

作者：

Sun, Xiao-Fang ^{[1
,2
,3
]}

Xiao, Xin-Hua ^{[1
,2
]}

Zhang, Zhen-Xin ^{[2
,4
]}

Liu, Ying ^{[5
]}

Xu, Tao ^{[6
,7
]}

Zhu, Xi-Lin ^{[5
]}

Zhang, Yun ^{[1
,2
]}

Wu, Xiao-Pan ^{[5
]}

Li, Wen-Hui ^{[1
,2
]}

Zhang, Hua-Bing ^{[1
,2
]}

Yu, Miao ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Diabet Res Ctr, Dept Endocrinol,Key Lab Endocrinol,Minist Hlth, Beijing 100730, Peoples R China

[2] Peking Union Med Coll, Beijing 100730, Peoples R China

[3] Qingdao Univ, Dept Endocrinol, Affiliated Hosp, Qingdao 266003, Shandong, Peoples R China

[4] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Neurol, Beijing 100730, Peoples R China

[5] Chinese Acad Med Sci, Natl Lab Med Mol Biol, Inst Basic Med Sci, Sch Basic Med,Peking Union Med Coll, Beijing 100730, Peoples R China

[6] Chinese Acad Med Sci, Dept Epidemiol & Stat, Inst Basic Med Sci, Beijing 100730, Peoples R China

[7] Peking Union Med Coll, Sch Basic Med, Beijing 100730, Peoples R China

来源：

CHINESE MEDICAL JOURNAL | 2015年 / 128卷 / 14期

基金：

中国国家自然科学基金;

关键词：

Birthweight; Chinese Han; Genetic Polymorphisms; Impaired Glucose Metabolism; GENETIC-VARIANTS; LOCI; GLUCOSE; HHEX;

D O I：

10.4103/0366-6999.160489

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 (beta = -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 (beta = -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.

引用

页码：1873 / 1878

页数：6

共 22 条

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PLOS ONE, 2014, 9 (03)

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