METHODS: The genotypes of TCF7L2, DEFB1 and CD14 polymorphism were determined in 240 nephrolithiasis patients and 240 healthy controls by restriction digestion method of PCR. The levels of serum TCF7L2, DEFB1, CD14, uric acid and other biochemical parameters were measured both in nephrolithiasis patients and healthy control.
RESULTS: The patients and control groups showed 30% and 50% 1654 AA DEFB1 genotype respectively. The Allele frequency in case of patient's group was 63.67% while in control group it was 36.33%. The mean serum DEFB1 levels of the patients and control groups attained were 115.66 and 239.43 pg/mL respectively. The allele frequency of TCF7L2 in patients and controls were 44.17% and 70.0% for C-allele, 55.83% and 30.00% for T-allele respectively. The mean of serum TCF7L2 levels were significantly decreased in patients compared to control group.
CONCLUSIONS: The present findings are first of its class that validates a considerable connection of DEFB1 and TCF7L2 gene polymorphisms with nephrolithiasis and could probably act as indicators to estimate the risk associated to nephrolithiasis.
METHODS: Literature was searched in multiple databases including PubMed, Web of Science, EMBASE (Ovid SP), Airiti Library, Medline Complete, and ProQuest up to July 2015. Allelic frequency for TCF7L2 rs7903146 polymorphism in GDM and control subjects was extracted and statistical analysis was performed using Comprehensive Meta-Analysis (CMA) 2.0 statistical software. The association between TCF7L2 rs7903146 polymorphism and GDM risk was assessed by pooled odd ratios (ORs) using five gene models (dominant, recessive, homozygote, heterozygote, and allele). Stratified analysis based on race/ethnicity was also conducted. The between-study heterogeneity and contribution of each single study to the final result was tested by Cochran Q test and sensitivity analyses, respectively. Publication bias was evaluated using Egger's linear regression test.
RESULTS: A total of 16 studies involving 4,853 cases and 10,631 controls were included in this meta-analysis. Significant association between the T-allele of rs7903146 and GDM risk was observed under all genetic models, dominant model (OR = 1.44, 95% CI = 1.19-1.74), recessive model (OR = 1.35, 95% CI = 1.08-1.70), heterozygous model (OR = 1.31, 95% CI = 1.12-1.53), homozygous model (OR = 1.67, 95% CI = 1.31-2.12), and allele model (OR = 1.31, 95% CI = 1.12-1.53). Stratified analysis by race/ethnicity showed a statistically significant association between rs7903146 polymorphism and susceptibility to GDM under homozygous genetic model (TT versus CC) among whites, Hispanics/Latinos and Asians. Sensitivity analysis showed that the overall findings were robust to potentially influential decisions of the 16 studies included. No significant evidence for publication bias was observed in this meta-analysis for overall studies and subgroup studies.
CONCLUSIONS: This meta-analysis showed that the T allele of TCF7L2 rs7903146 polymorphism was associated with susceptibility of GDM in overall population in white, Hispanic/Latino and Asian sub-groups. Asians with homozygous TT allele of rs7903146 polymorphism have highest risk of GDM (OR = 2.08) followed by Hispanics/Latinos (OR = 1.80) and whites (OR = 1.51). The highest and lowest frequency of T allele of rs7903146 was found in Malaysia and South Korea, respectively. Future studies are needed to profile genetic risk for GDM among high risk Asian and Pacific Islander subgroups.
Methods: A targeted GWAS was used to investigate whether ten candidate genes with known roles in corneal development were associated with CCT in two Singaporean populations. The single nucleotide polymorphisms (SNPs) within a 500 kb interval encompassing each candidate were analyzed, and in light of the resulting data, members of the Wnt pathway were subsequently screened using similar methodology.
Results: Variants within the 500 kb interval encompassing three candidate genes, DKK1 (rs1896368, p=1.32×10-3), DKK2 (rs17510449, p=7.34×10-4), and FOXO1 (rs7326616, p=1.56×10-4 and rs4943785, p=1.19×10-3), were statistically significantly associated with CCT in the Singapore Indian population. DKK2 was statistically significantly associated with CCT in a separate Singapore Malaysian population (rs10015200, p=2.26×10-3). Analysis of Wnt signaling pathway genes in each population demonstrated that TCF7L2 (rs3814573, p=1.18×10-3), RYK (rs6763231, p=1.12×10-3 and rs4854785, p=1.11×10-3), and FZD8 (rs640827, p=5.17×10-4) were statistically significantly associated with CCT.
Conclusions: The targeted GWAS identified four genes (DKK1, DKK2, RYK, and FZD8) with novel associations with CCT and confirmed known associations with two genes, FOXO1 and TCF7L2. All six participate in the Wnt pathway, supporting a broader role for Wnt signaling in regulating the thickness of the cornea. In parallel, this study demonstrated that a hypothesis-driven candidate gene approach can identify associations in existing GWAS data sets.