Association of a type 2 diabetes genetic risk score with insulin secretion modulated by insulin sensitivity among Chinese Hans

Kong, Xiaomu; Hong, Jing; Zhang, Xuelian; Yang, Wenying

doi:10.1111/cge.12817

Cited by 13 publications

(15 citation statements)

References 44 publications

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“…In a follow‐up study among Finnish men, a non‐weighted GRS for type 2 diabetes and a weighted GRS for FPG and IR were associated with incident type 2 diabetes . Similar results have been found in Asian populations, with Korean adults with a higher GRS having higher type 2 diabetes risk and a tendency for impaired insulin secretion among a Chinese Han population . In the present study, significant results were found between GRS or weighted GRS and FPG among female subjects.…”

Section: Discussionsupporting

confidence: 87%

“…63 Similar results have been found in Asian populations, with Korean adults with a higher GRS having higher type 2 diabetes risk 64 and a tendency for impaired insulin secretion among a Chinese Han population. 65 In the present study, significant results were found between GRS or weighted GRS and FPG among female subjects. Significant results were also found between GRS or weighted GRS and diabetes among male subjects.…”

Section: Discussionsupporting

confidence: 48%

“…63 Other Asian population studies did not consider sex differences. 64,65 Sex differences may need to be confirmed in future studies. The present study has several strengths.…”

Section: Discussionmentioning

confidence: 98%

“…A study conducted in Finland only explored the association between diabetes risk and GRS in men . Other Asian population studies did not consider sex differences . Sex differences may need to be confirmed in future studies.…”

Section: Discussionmentioning

confidence: 99%

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Effects of variants of 50 genes on diabetes risk among the Chinese population born in the early 1960s

Song

Wang

Fang

et al. 2019

Journal of Diabetes

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BackgroundGenome‐wide association studies have identified loci that significantly increase diabetes risk. This study explored the genetic susceptibility in relation to diabetes risk in adulthood among a Chinese population born in the early 1960s.MethodsIn all, 2129 subjects (833 males, 1296 females) were selected from the cross‐sectional 2010 to 2012 China National Nutrition and Health Survey. Fifty diabetes‐related single nucleotide polymorphisms (SNPs) were detected. Two diabetes genetic risk scores (GRSs) based on the 50 diabetes‐predisposing variants were developed to examine the association of these SNPs with diabetes risk.ResultsAssociations were found between diabetes risk and SNPs in the MTNR1B (rs10830963), KLHDC5 (rs10842994), GRK5 (rs10886471), cyclindependentkinase 5 regulatory subunit associated protein 1 (rs10946398), adaptorrelated protein complex 3 subunit sigma 2 (rs2028299), diacylglycerol kinase beta/transmembrane protein 195 (rs2191349), SREBF chaperone (rs4858889), ankyrin1 (rs516946), RAS guanyl releasing protein 1 (rs7403531), and zinc finger AN1‐type containing 3 (rs9470794) genes. As a continuous variable, with a 1‐point increase in the GRS or weighted (w) GRS, fasting plasma glucose (FPG) increased 0.045 and 0.044 mM, respectively (P < 0.001 for both), after adjusting for confounders. Both GRS and wGRS showed an association with diabetes, with a multivariable‐adjusted odds ratio (95% confidence interval) of 1.09 (1.00‐1.19) and 1.12 (1.03‐1.22), respectively, among all subjects. No significant associations were found between the GRS or wGRS and impaired fasting glucose or impaired glucose tolerance.ConclusionsThe data suggest the association of 10 SNPs and the GRS or wGRS with diabetes risk. Genetic susceptibility to diabetes may synergistically affect the risk of diabetes in adulthood.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 48%

“…63 Other Asian population studies did not consider sex differences. 64,65 Sex differences may need to be confirmed in future studies. The present study has several strengths.…”

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of variants of 50 genes on diabetes risk among the Chinese population born in the early 1960s

Song

Wang

Fang

et al. 2019

Journal of Diabetes

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show abstract

“…Each participant completed a standard 75-g oral glucose tolerance test after overnight fasting. Blood samples were drawn at 0 and 30 min and 2 h after the oral glucose tolerance test for measurement of plasma glucose and serum insulin concentrations as described previously [19]. …”

Section: Methodsmentioning

confidence: 99%

Sexual Dimorphism of a Genetic Risk Score for Obesity and Related Traits among Chinese Patients with Type 2 Diabetes

et al. 2019

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Background: Obesity is more prevalent in men than in women in China, especially within the middle-aged population. Objectives: The present study aims to determine the contribution of sexual dimorphisms to obesity and related traits in terms of the mechanisms involving the obesity-related genetic variants among patients of Chinese Han ancestry with type 2 diabetes. Method: In the Chinese National Diabetes and Metabolic Disorders Study, 2,555 out of 4,036 patients with type 2 diabetes were treatment naive, including 1,142 men and 1,413 women. Single-nucleotide polymorphisms (SNP) from 18 genomic loci previously found to be associated with obesity-related traits were successfully genotyped, and a genetic risk score (GRS) was constructed by summing the risk alleles for obesity. Results: Single SNP analysis showed that genetic variants in SLC30A10, TMEM18, GNPDA2, PRL, TFAP2B, BDNF, MTCH2, FTO, and MC4R were nominally associated with waist circumference (WC), BMI, and risk for abdominal or general obesity in the untreated patients with type 2 diabetes, as well as in the total group of patients with type 2 diabetes (untreated and treated) (p < 0.05). Interactions between sex and SNP in PRL, MTCH2,and FTO were detected (p < 0.05). In the untreated patients with diabetes, the GRS was nominally associated with WC (β = 0.0032, SE = 0.0011; p = 0.003), BMI (β = 0.0030, SE = 0.0013; p = 0.027), and increased risk for abdominal (OR = 1.08; 95% CI 1.02–1.13; p = 0.004) or general obesity (OR = 1.07; 95% CI 1.02–1.13; p = 0.011) in men but not in women. GRS-sex interactions were detected in the determinant of WC (p = 0.019) and abdominal obesity (p = 0.016). Among patients aged 30–60 years, GRS was found to be significantly associated with WC (β = 0.0050, SE = 0.0016; p = 0.002) and abdominal obesity (OR = 1.10; 95% CI 1.04–1.17; p = 0.001) and nominally associated with BMI (β = 0.0057, SE = 0.0020; p = 0.005) and general obesity (OR = 1.07; 95% CI 1.01–1.14; p = 0.027) in men, whereas in women none of the associations were detected. GRS-sex interactions were present in the determinant of WC (p = 0.015), BMI (p = 0.032), and abdominal obesity (p = 0.012). Among patients aged 60 years or older, neither an association of GRS with obesity-related traits nor GRS-sex interactions were detected. Conclusions: Genetic factors contribute to obesity-related traits in a sex-dependent pattern among middle-aged Chinese, and men tend to be more susceptible to the genetic risk of obesity.

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Genetic variants in promoter regions associated with type 2 diabetes mellitus: A large‐scale meta‐analysis and subgroup analysis

Wang

2019

J of Cellular Biochemistry

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Background: Promoter plays important roles in regulating transcription of genes. Association studies of genetic variants in promoter region with type 2 diabetes (T2D) risk have been reported, but most were limited to small number of individual genetic variants and insufficient sample sizes. In addition, the effect of study populations and demographic characteristics were often neglected.Methods: In this study, we conducted a large-scale meta-analysis and subgroup analysis of T2D associated genetic variants in the promoter regions to evaluate their contribution to the susceptibility in T2D. Alleles and genotypes from cohort or case-controlled studies were extracted for future study. Total 41 742 cases and 50 493 controls for three loci were involved in 70 articles.Results: Seventy case-controlled studies of three genes with 41 742 cases and 50 493 controls were included. Meta-analysis showed only rs266729 and rs17300539 of ADIPOQ, and rs1884613, rs2144908, and rs4810424 of HNF4A were significantly associated with T2D risk. Subgroup analysis showed that both rs266729 and rs17300539 of ADIPOQ were associated with the risk of T2D in Caucasian population, but only rs266729 of ADIPOQ in Asian population and rs2144908 in other population including multinational North American. For diagnostic criteria, rs266729 of ADIPOQ and rs2144908 of HNF4A were associated with T2D risk when WHO/ADA diagnostic criteria were used. For genotyping methods, both rs266729 of ADIPOQ and rs2144908 of HNF4A were associated with T2D risk when other than Taqman and Sequencing methods were used. Conclusions: T2D was significantly associated with promoter rs266729, rs17300539, rs1884613, rs2144908, and rs4810424, and the association of T2D risk were affected by study population, diagnostic criteria, and genotype methods. K E Y W O R D S genetic variant, promoter, type 2 diabetes J Cell Biochem. 2019;120:13012-13025. wileyonlinelibrary.com/journal/jcb 13012 |

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Association of a type 2 diabetes genetic risk score with insulin secretion modulated by insulin sensitivity among Chinese Hans

Cited by 13 publications

References 44 publications

Effects of variants of 50 genes on diabetes risk among the Chinese population born in the early 1960s

Effects of variants of 50 genes on diabetes risk among the Chinese population born in the early 1960s

Sexual Dimorphism of a Genetic Risk Score for Obesity and Related Traits among Chinese Patients with Type 2 Diabetes

Genetic variants in promoter regions associated with type 2 diabetes mellitus: A large‐scale meta‐analysis and subgroup analysis

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