Analysis Of Shared Risk Factors DGKH And FGFR2 Genes With Schizophrenia, Bipolar Disorder Major Depressive A Meta-analysis NOS3 Gene Diabetic Nephropathy

We carried out a large scale case-control study to test the association between two genes: DGKH and FGFR2 and three major mental disorders: schizophrenia (SCZ), bipolar disorder (BPD) and major depressive disorder (MDD) in the Chinese Han population.Diacylglycerol kinase eta (DGKH) is the first BPD susceptible gene introduced by genome-wide association study (GWAS). It is localized in BPD and SCZ linkage region 13q14, and encodes an importance protein in the lithium sensitive phosphatidyl inositol signaling pathway. 13 tag single nucleotide polymorphisms (SNPs) were genotyped using Taqman assay in 1139 BPD patients (including 645 type I BPD), 1122 SCZ patients, 1122 MDD patients and 1138 healthy controls. One SNP (rs2122246) was associated with type I BPD, and another SNP (rs1170099) was associated with SCZ. We also found a strong haplotypic association for both of the two disorders. Our results supported that DGKH was a shared risk factor of both BPD and SCZ in the Chinese Han population. Fibroblast growth factor receptor 2 (FGFR2) is located in 10q25-26, a SCZ and BPD linkage region. It was firstly suspected as a risk gene for SCZ because a nearby SNP showed strong association with SCZ in a GWAS and then in a huge meta-analysis of replication studies. We genotyped 8 SNPs using Taqman assay in 1139 BPD patients, 1112 SCZ patients, 1119 MDD patients and 1135 healthy controls. We found one SNP, rs11199993, and a haplotype including this SNP, showed positive association with BPD. There is a nearly missense variant in high linkage disequilibrium with this SNP, so it is worthy of further studies.Potential population stratification in our samples was analyzed using additional random 65 SNPs dispersed on different chromosomes. We demonstrated that our findings should not be caused by population stratification.A number of association studies have investigated the role of the nitric oxide synthase 3 (NOS3) gene in the development of diabetic nephropathy (DN). However, results have been inconclusive. We performed a meta-analysis of 28 association studies focusing on three polymorphisms in the NOS3 gene (G894T (Glu289Asp), 4b/a, and T-786C) and the risk of DN published before July 2009, covering a total of 10,364 subjects. Although significant heterogeneity was initially found in the analysis of G894T, it did not remain when analysis was done by ethnic subgroups. 894T was negatively associated with DN in Caucasian populations of European origin, but was positively associated with DN in East Asian and other populations. Association of the 4b/a variant was observed when studies involving microalbuminuria were excluded. The T-786C variant showed an overall weak association. Our meta-analysis of the effect of NOS3 gene polymorphisms on the risk of DN supports the involvement of the NOS3 gene in the pathogenesis of DN.