Positive association between variations in CDKAL1 and type 2 diabetes in Han Chinese individuals

Liu, Y.; Yu, Lan; Zhang, Di; Chen, Zhi; Zhou, Daizhan; Zhao, Teng; Li, S.; Wang, Ting; Hu, Xun; Gao, Feng; Zhang, Z. F.; He, Lin; Xu, Hao

doi:10.1007/s00125-008-1141-6

Cited by 43 publications

(30 citation statements)

References 9 publications

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“…Based on HapMap CHB database, rs4712523 was in very high LD with rs10946398, rs7754840 and rs10440833 (r 2 ¼1.0, 1.0 and 0.82, respectively), which all showed associations with T2D risk both in European GWAS and in Chinese replication studies. 19,[25][26][27][28] Abbreviations: BMI, body mass index; HDL, high-density lipoprotein cholesterol. a t-tests and w 2 -tests were used for continuous or categorical variables, respectively, in combined population.…”

Section: Discussionmentioning

confidence: 99%

Genetic variants on chromosome 6p21.1 and 6p22.3 are associated with type 2 diabetes risk: a case–control study in Han Chinese

Qian

et al. 2012

J Hum Genet

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Section: Discussionmentioning

confidence: 99%

Genetic variants on chromosome 6p21.1 and 6p22.3 are associated with type 2 diabetes risk: a case–control study in Han Chinese

Qian

et al. 2012

J Hum Genet

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“…This study population had been used and described in our previous study. 10 Diabetes status was defined in accordance with WHO criteria and the details of the subgroups are summarized in Table 1 (Materials and Methods).…”

Section: Materials and Methods Participantsmentioning

confidence: 99%

Common variants near TERC are associated with leukocyte telomere length in the Chinese Han population

Shen

Zhou

et al. 2011

Eur J Hum Genet

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A recent genome-wide association study has identified an association between leukocyte telomere length (LTL) and a locus at 3q26 that includes TERC. In order to evaluate the effects of the SNPs rs12696304 and rs16847897 near TERC in the population of mainland China, we conducted an association study of LTL focusing on these two candidate SNPs in a sample of 4016 Chinese Han individuals. Multiple linear regression analyses were performed to evaluate the association of LTL with each SNP adjusted for age, gender and diabetes status. In the study, we confirmed the association of SNP rs12696304 and rs16847897 near TERC with LTL in the Chinese Han population (PB4.5Â10 À3 and 9.5Â10 À5 , respectively). Each copy of the major allele of rs12696304 and rs16847897 was associated with a shorter mean telomere length of 0.024 and 0.031 T/S respectively, which is equivalent to about 3 and 4 years of average age-related telomere attrition. Our short report confirmed the effects of SNPs near TERC on LTL in the Chinese Han population for the first time. Keywords: Chinese population; TERC; leukocyte telomere length INTRODUCTIONTelomeres are structures at the ends of eukaryotic chromosomes, which are made up of a repetitive sequence and which has a major role in genomic stability. Telomere dysregulation can lead to cell death, cell senescence, or abnormal cell proliferation. 1 In humans, leukocyte telomere length (LTL) is getting shorter progressively with age, and is frequently reported to be relatively shorter in aging-related diseases: such as Alzheimer's disease 2 and vascular dementia. 3 Telomere length varies between individuals of the same age, and is found to be inheritable in quantitative-trait linkage analyses of sib pairs. 4,5 Quantitative trait locus studies have mapped putative loci for telomere length to human chromosomes 3p26.1, 10q26.13, 12q12.22 and 14q23.2. [5][6][7] Telomerase is a large, mainly uncharacterized, RNA-protein complex that is responsible for the de novo synthesis and maintenance of telomere ends. TERC is a main component of telomerase, which serves as a template for addition of multiple 6 bp (TTAGGG) telomere repeats. A recent genome-wide association study (GWAS) identified association of common variants near TERC (on 3q26) with telomere length in two large European cohorts of 2917 individuals, followed by replication in three further European cohorts of 9492 individuals. 8 The strongest associations with LTL were observed for SNP rs12696304 and rs16847897 near TERC on 3q26, and the association signals across the 3q26 locus between rs12696304 and rs16847897 are located toward opposite ends of an B87 kb region showing significant

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“…20 An interview was conducted by trained physicians or public health workers from the Pudong and Baoshan Centers for Disease Control and Prevention. The study individuals need to meet the following two criteria: (1) they were stable residents in the areas and (2) they were free from severe psychological disorders, physical disabilities and diagnosed with cancer, tuberculosis, AIDS and other communicable diseases within 6 months.…”

Section: Materials and Methods Participantsmentioning

confidence: 99%

“…Moreover, more than 50% of type 2 diabetes patients were diagnosed at the age of 45-65 years and have 5-15 years duration of disease. In all, 2041 controls (635 men, 1406 women; age 58.1 ± 9.4 years), 4,20,21 with a FPG concentration o6.1 mmol l À1 , were enrolled from the same geographical area with cases. The overall age and sex distribution of controls were matched with that of case group.…”

Section: Materials and Methods Participantsmentioning

confidence: 99%

Variations in/nearby genes coding for JAZF1, TSPAN8/LGR5 and HHEX-IDE and risk of type 2 diabetes in Han Chinese

et al. 2010

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Several genetic loci (JAZF1, CDC123/CAMK1D, TSPAN8/LGR5, ADAMTS9, VEGFA and HHEX-IDE) were identified to be significantly related to the risk of type 2 diabetes and quantitative metabolic traits in European populations. Here, we aimed to evaluate the impacts of these novel loci on type 2 diabetes risk in a population-based case-control study of Han Chinese (1912 cases and 2041 controls). We genotyped 13 single-nucleotide polymorphisms (SNPs) in/near these genes and examined the differences in allele/genotype frequency between cases and controls. We found that both IDE rs11187007 and HHEX rs1111875 were associated with type 2 diabetes risk (for both variants: odds ratio (OR)¼1.15, 95% confidence interval (CI) 1.04-1.28, P¼0.009). In a meta-analysis where we pooled our data with the three previous studies conducted in East Asians, we found that the variants of JAZF1 rs864745 (1.09 (1.03-1.16); P¼3.49Â10 À3 ) and TSPAN8/LGR5 rs7961581 (1.11 (1.05-1.17); P¼1.89Â10 À4 ) were significantly associated with type 2 diabetes risk. In addition, the meta-analysis (7207 cases and 8260 controls) also showed that HHEX rs1111875 did have effects on type 2 diabetes in Chinese population (OR¼1.15(1.10-1.21); P¼1.93Â10 À8 ). This large population-based study and meta-analysis further confirmed the modest effects of the JAZF1, TSPAN8/LGR5 and HHEX-IDE loci on type 2 diabetes in Chinese and other East Asians.

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Positive association between variations in CDKAL1 and type 2 diabetes in Han Chinese individuals

Cited by 43 publications

References 9 publications

Genetic variants on chromosome 6p21.1 and 6p22.3 are associated with type 2 diabetes risk: a case–control study in Han Chinese

Genetic variants on chromosome 6p21.1 and 6p22.3 are associated with type 2 diabetes risk: a case–control study in Han Chinese

Common variants near TERC are associated with leukocyte telomere length in the Chinese Han population

Variations in/nearby genes coding for JAZF1, TSPAN8/LGR5 and HHEX-IDE and risk of type 2 diabetes in Han Chinese

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