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Aims: The common copy number variant (CNV) in the haptoglobin (Hp) gene may influence the susceptibility to diabetic macrovascular diseases. We aimed to investigate the relationship of the genetic variant rs2000999, located in the haptoglobin-related protein (HPR) gene, with serum Hp levels and diabetic macrovascular diseases in Chinese type 2 diabetes patients., Methods: The Hp CNV and rs2000999 were genotyped in a group of 5457 Chinese patients with type 2 diabetes. Associations of rs2000999 with the common Hp CNV, susceptibility to diabetic macrovascular diseases and related metabolic traits were analysed. Furthermore, 886 patients were selected to detect serum Hp levels and to evaluate the correlation between rs2000999 and serum Hp levels., Results: The genetic variant rs2000999 was not associated with diabetic macrovascular diseases (P = 0.6109), while subjects carrying the A allele had higher levels of low-density lipoprotein cholesterol (P = 0.0578) and a smaller inter-adventitial diameter of the common carotid artery (P = 0.0266). Additionally, rs2000999 exhibited strong association with serum Hp levels (P = 2.03 × 10 -21 )., Conclusions: The genetic variant rs2000999 was not associated with diabetic macrovascular diseases but showed an association with metabolic traits and serum Hp levels in Chinese patients with type 2 diabetes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aim: We aimed to investigate the association between uric acid related genetic loci and DKD susceptibility in type 2 diabetes patients., Methods: Seventeen single nucleotide polymorphisms (SNPs) from thirteen loci related to serum uric acid were genotyped in 2,892 type 2 diabetes patients. Associations between SNPs and uric acid, SNPs and quantitative traits related to DKD or its susceptibility were evaluated., Results: In this study, uric acid showed a strong association with DKD (OR=1.006, p<0.0001). GCKR rs780094, SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142, SLC22A12 rs505802 and NRXN2 rs506338 were positively associated with serum uric acid (p=3.79E-05, 0.0002, 2.04E-10, 2.23E-09, 0.0018 and 0.0015, respectively). SLC2A9 rs11722228 and SF1 rs606458 were significantly associated with DKD (OR=0.864, p=0.0440; OR=1.223, p=0.0038). SLC2A9 rs3775948 and ABCG2 rs2231142 were associated with DKD marginally (OR=0.878, p=0.0506; OR=0.879, p=0.0698). SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142 and SF1 rs606458 were significantly associated with the estimated glomerular filtration rate (p=0.0005, 0.0006, 0.0003, and 0.0424, respectively)., Conclusions: Our study indicated that the uric acid related alleles of SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142 might affect DKD susceptibility and possibly through non-uric acid pathway in the Chinese people with type 2 diabetes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Genome-wide association studies (GWAS) have uncovered numerous variants associated with body mass index (BMI), waist circumference, and waist-to-hip ratio. Our study aims to investigate how these variants are linked to fat distribution. We genotyped 56 validated variants of BMI, waist circumference, and waist-to-hip ratio in 2958 subjects from Chinese community-based populations and performed linear regression analyses to determine the association with visceral fat area (VFA) and subcutaneous fat area (SFA) imaged by magnetic resonance imaging (MRI). We found rs671 in ALDH2 exhibited the significant associations with VFA and the VFA-SFA ratio in all subjects (P = 9.64 × 10(-5) and 6.54 × 10(-4)). rs17782313 near MC4R for VFA and rs4846567 near LYPLAL1 for SFA were found in females only (P = 2.93 × 10(-4) and 0.0015), whereas rs671 in ALDH2 for VFA and the VFA-SFA ratio was restricted to males (P = 1.75 × 10(-8) and 4.43 × 10(-8)). Given the robust association of rs671 with alcohol consumption, we next demonstrated the primary effects of rs671 on VFA and the VFA-SFA ratio were restricted to drinkers (P = 1.45 × 10(-4) and 4.65 × 10(-3)). Our data implied that variants of MC4R and LYPLAL1 modulated body fat distribution with sexual dimorphism and that alcohol consumption may mediate the impact of the ALDH2 locus on visceral fat in a Chinese population.

Aims/hypothesis: Three recent genome-wide association studies (GWAS) identified several single-nucleotide polymorphisms (SNPs) with modest effects on diabetic retinopathy in Mexican-American and white patients with diabetes. This study aimed to evaluate the effects of these variants on diabetic retinopathy in Chinese patients with type 2 diabetes., Methods: A total of 1,972 patients with type 2 diabetes were recruited to this study, including 819 patients with diabetic retinopathy and 1,153 patients with diabetes of ≥5 years duration but without retinopathy. Forty SNPs associated with diabetic retinopathy in three GWAS were genotyped. Fundus photography was performed to diagnose and classify diabetic retinopathy., Results: rs17684886 in ZNRF1 and rs599019 near COLEC12 were associated with diabetic retinopathy (OR 0.812, p = 0.0039 and OR 0.835, p = 0.0116, respectively) and with the severity of diabetic retinopathy (p = 0.0365 and p = 0.0252, respectively, for trend analysis). Sub-analysis in patients with diabetic retinopathy revealed that rs6427247 near SCYL1BP1 (also known as GORAB) and rs899036 near API5 were associated with severe diabetic retinopathy (OR 1.368, p = 0.0333 and OR 0.340, p = 0.0005, respectively). The associations between rs6427247 and rs899036 and severe diabetic retinopathy became more evident after a meta-analysis of published GWAS data (OR 1.577, p = 2.01 × 10(-4) for rs6427247; OR 0.330, p = 5.84 × 10(-7) for rs899036)., Conclusions/interpretation: We determined that rs17684886 and rs599019 are associated with diabetic retinopathy and that rs6427247 and rs899036 are associated with severe diabetic retinopathy in Chinese patients with type 2 diabetes.

Background: Diabetic retinopathy (DR) is an important microvascular complication of diabetes with a high concordance rate in patients with diabetes. Inflammation is supposed to participate in the development of DR. This study aimed to investigate whether genetic variants of CRP are associated with DR., Methods: A total of 1,018 patients with type 2 diabetes were recruited in this study. Of these patients, 618 were diagnosed with DR, 400 were patients with diabetes for over 10 years but without DR, considered as cases and controls for DR, respectively. Four tagging SNPs (rs2808629, rs3093077, rs1130864 and rs2808634) within CRP region were genotyped for all the participants. Fundus photography was performed for diagnosis and classification for DR., Results: rs2808629 was significantly associated with increased susceptibility to DR (odds ratio 1.296, 95% CI 1.076-1.561, P = 0.006, empirical P = 0.029, for G allele). This association remained significant after adjustment for confounding factors (odds ratio 1.261, 95% CI 1.022-1.555, P = 0.030)., Conclusions: In this study, we found CRP rs2808629 was associated with DR in the Chinese patients with type 2 diabetes.

Background: Elevated serum uric acid concentration is an independent risk factor and predictor of type 2 diabetes (T2D). Whether the uric acid-associated genes have an impact on T2D remains unclear. We aimed to investigate the effects of the uric acid-associated genes on the risk of T2D as well as glucose metabolism and insulin secretion., Method: We recruited 2,199 normal glucose tolerance subjects from the Shanghai Diabetes Study I and II and 2,999 T2D patients from the inpatient database of Shanghai Diabetes Institute. Fifteen single nucleotide polymorphisms (SNPs) mapped in or near 11 loci (PDZK1, GCKR, LRP2, SLC2A9, ABCG2, LRRC16A, SLC17A1, SLC17A3, SLC22A11, SLC22A12 and SF1) were genotyped and serum biochemical parameters related to uric acid and T2D were determined., Results: SF1 rs606458 showed strong association to T2D in both males and females (p = 0.034 and 0.0008). In the males, LRRC16A was associated with 2-h insulin and insulin secretion (p = 0.009 and 0.009). SLC22A11 was correlated with HOMA-B and insulin secretion (p = 0.048 and 0.029). SLC2A9 rs3775948 was associated with 2-h glucose (p = 0.043). In the females, LRP2 rs2544390 and rs1333049 showed correlations with fasting insulin, HOMA-IR and insulin secretion (p = 0.028, 0.033 and 0.052 and p = 0.034, 0.047 and 0.038, respectively). SLC2A9 rs11722228 was correlated with 2-h glucose, 2-h insulin and insulin secretion (p = 0.024, 0.049 and 0.049, respectively)., Conclusions: Our results indicated that the uric acid-associated genes have an impact on the risk of T2D, glucose metabolism and insulin secretion in a Chinese population.