Abstract
Background: More than 60 genetic susceptibility loci associated with type 2 diabetes mellitus (T2DM) have been established in populations of Asian and European ancestry. Given ethnic differences and environmental factors, validation of the effects of genetic risk variants with reported associations identified by Genome-Wide Association Studies (GWASs) is essential. The study aims at evaluating the associations of T2DM with 29 single nucleotide polymorphisms (SNPs) from 19 candidate genes derived from GWASs in a northern Han Chinese population. Method: In this case-control study, 461 T2DM-diagnosed patients and 434 controls were recruited at the Jidong oil field hospital (Hebei, China) from January 2009 to October 2013. A cumulative genetic risk score (cGRS) was calculated by summation of the number of risk alleles, and a weight GRS (wGRS) was calculated as the sum of risk alleles at each locus multiplied by their effect sizes for T2DM, using the independent variants selected. Result: The allelic frequency of the “A” allele at rs17106184 (Fas-associated factor 1, FAF1) was significantly higher in the T2DM patients than that of the healthy controls (11.7% vs. 6.4%, p < 0.001). Individuals in the highestquartile of wGRS had an over three-fold increased risk for developing T2DM compared with those in the lowest quartile (odds ratio = 3.06, 95% CI = 1.92–4.88, p < 0.001) adjusted for age, sex, BMI, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP). The results were similar when analyzed with the cGRS. Conclusions: We confirmed the association between rs17106184 (FAF1) and T2DM in a northern Han Chinese population. The GRS calculated based on T2DM susceptibility variants may be a useful tool for predicting the T2DM susceptibility.
Highlights
Type 2 diabetes mellitus (T2DM) has been identified as a major international health challenge which has a great worldwide impact on morbidity, premature mortality, and economic burden [1].In China, the prevalence of diabetes increased from 0.9% in 1980 to 11.6% in 2013, indicating that there were approximately 113.9 million Chinese adults suffering from diabetes [2]
After excluding one single nucleotide polymorphisms (SNPs) due to its deviation from Hardy-Weinberg equilibrium (HWE), associations between 28 SNPs and type 2 diabetes mellitus (T2DM) risks were assessed using odds ratios (ORs) with 95% CIs and p value derived from unconditional logistic regression (ULR) analyses adjusted for age, sex, Body mass index (BMI), TG, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP)
Fas-associated factor 1 (FAF1) was significantly associated with T2DM, even after adjusting for age, sex, BMI, TC, TG, LDL-C, SBP, and DBP (adjusted odds ratio (AOR) = 2.22, 95% CI = 1.53–3.24, p < 0.0001)
Summary
Type 2 diabetes mellitus (T2DM) has been identified as a major international health challenge which has a great worldwide impact on morbidity, premature mortality, and economic burden [1]. The association is inconsistent in terms of risk allele frequencies and odds ratios (ORs) among these populations. Another fat mass and obesity associated SNP rs8050136 (FTO) was associated with T2DM in UK samples [7], whereas it was not found to be associated with T2DM in Chinese samples [16]. Combining multiple T2DM-related loci with modest effects using a genetic risk score (GRS) may be useful in the risk stratification of T2DM [18,19].
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