Abstract P236: Association of Obesity-related Genomic Loci and Type 2 Diabetes among Chinese Population

Obesity is one of the most important risk factors for type 2 diabetes (T2D). The aim of this study is to examine the associations between established obesity-related genomic loci and T2D as well as multiple quantitative glycemic traits among Chinese population. Single nucleotide polymorphisms (SNPs) near or within genes NEGR1 , SEC16B , TMEM18 , ETV5/DGKG , BAT2 , BDNFOS , BDNF , FAIM2 , MC4R , KCTD15 , MTCH2 , GNPDA2 , NPC1 , MAF , PTER , PRL , PCSK1 , PFKP , CTNNBL1 , NRXN3 , MSRA , SLC30A10 and TFAP2B from 23 independent genomic loci were genotyped among 5,338 T2D patients and 4,663 controls. An additive genetic model was assumed. Logistic and linear regression models were used to examine the associations of these genomic loci with T2D and glycemic traits, respectively. Two SNPs near MC4R (rs12970134) and GNPDA2 (rs10938397) genes were significantly associated with T2D after adjusting for age and gender (OR [95% CI] = 1.14 [1.06, 1.22] for per A allele of rs12970134, P = 4.75х10 -4 ; OR [95% CI] = 1.10 [1.03, 1.17] for per G allele of rs10938397, P = 4.54х10 -3 ). When body mass index (BMI) and waist circumference was further adjusted for in logistic regression models, the association of MC4R with T2D maintained significant (OR [95% CI] = 1.10 [1.02, 1.20], P = 1.81х10 -2 ) and that of GNPDA2 attenuated to non-significance (OR [95% CI] = 1.06 [0.98, 1.14], P = 1.26х10 -1 ). In addition, eight loci (near or within SEC16B , BDNF , KCTD15 , MAF , PRL , PCSK1 , CTNNBL1 and NRXN3 genes) showed significant associations with quantitative glycemic traits in the controls even after adjusting for BMI and waist circumference ( P < 0.05). For example, the G allele of SNP rs10146997 in the NRXN3 gene was associated with higher fasting insulin level (β [SE] = 0.064 [0.026], P = 1.31х10 -2 ), HOMA-IR (β [SE] = 0.064 [0.027], P = 1.71х10 -2 ) and lower insulin sensitivity (assessed by Matsuda index, β [SE] = -0.051 [0.026], P = 4.67х10 -2 ) compared to the A allele. The T allele of SNP rs6013029 in the CTNNBL1 was associated with greater fasting insulin(β [SE] = 0.098 [0.038], P = 1.02х10 -2 ), HOMA-IR (β [SE] = 0.100 [0.039], P = 1.13х10 -2 ) and HOMA-B (β [SE] = 0.104 [0.053], P = 4.73х10 -2 ), as well as lower insulin sensitivity (β [SE] = -0.096 [0.039], P = 1.47х10 -2 ) compared to G allele, suggesting its potential role in insulin resistance. In conclusion, these data suggest that these obesity-related genomic loci may be associated with T2D and glycemic traits after accounting for BMI and waist circumference among Chinese population.