Purpose To investigate the effects of genetic factors on idiopathic scoliosis (IS) and genetic modes through genetic epidemiological survey on IS in Chongqing City, China, and to determine whether SH3GL1, GADD45B, and FGF22 in the chromosome 19p13.3 are the pathogenic genes of IS through genetic sequence analysis. Methods 214 nuclear families were investigated to analyse the age incidence, familial aggregation, and heritability. SH3GL1, GADD45B, and FGF22 were chosen as candidate genes for mutation screening in 56 IS patients of 214 families. The sequence alignment analysis was performed to determine mutations and predict the protein structure. Results The average age of onset of 10.8 years suggests that IS is a early onset disease. Incidences of IS in first-, second-, third-degree relatives and the overall incidence in families (5.68%) were also significantly higher than that of the general population (1.04%). The U test indicated a significant difference, suggesting that IS has a familial aggregation. The heritability of first-degree relatives (77.68 ±10.39%), seconddegree relatives (69.89 ±3.14%), and third-degree relatives (62.14 ±11.92%) illustrated that genetic factors play an important role in IS pathogenesis. The incidence of firstdegree relatives (10.01%), second-degree relatives (2.55%) and third-degree relatives (1.76%) illustrated that IS is not in simple accord with monogenic Mendel's law but manifests as traits of multifactorial hereditary diseases. Sequence alignment of exons of SH3GL1, GADD45B, and FGF22 showed 17 base mutations, of which 16 mutations do not induce open reading frame (ORF) shift or amino acid changes whereas one mutation (C→T)occurred in SH3GL1 results in formation of the termination codon, which induces variation of protein reading frame. Prediction analysis of protein sequence showed that the SH3GL1 mutant encoded a truncated protein, thus affecting the protein structure. Conclusion IS is a multifactorial genetic disease and SH3GL1 may be one of the pathogenic genes for IS.
ABSTRACT. We explored the interaction of 6 candidate genetic mutations in essential hypertension (EH). The mutations AGT M235T, ACE I/D, eNOS Glu298Asp, ET-2 A985G, ANP T2238C, and NPRC A-55C were detected using a genechip microarray in 100 patients with EH and 97 controls from the Han population living in the Yunnan Province of China. Risks of EH were evaluated with respect to a combination of these genotypes. Interactions were analyzed using multifactor dimensionality reduction (MDR). P values were corrected using Bonferroni's adjustment. Results showed that CC genotype frequencies for NPRC A-55C (0.540) in EH were significantly higher than those in controls (0.237, P c < 0.01; odds ratio (OR) = 3.777; 95% confidence interval (CI) = 2.050-6.960). The OR for NPRC A-55C CC combined with ET-2 A985G GG increased to 4.673 and to 5.529 when the MT genotype of AGT M235T, the EE genotype of eNOS Glu298Asp, the GG genotype of ET-2 A985G, and the CC genotype of NPRC A-55C were combined. MDR showed that ET-2/NPRC is the best model (OR = 4.002; 95%CI = 2.1597-7.4159). The CC genotype for NPRC A-55C and the G allele for ET-2 A985G were associated with susceptibility to EH. Although the contributions of the candidate genes differ, they may have cooperative effects on conferring risk for EH. Moreover, potential gene-gene interactions were found between ET-2 A985G and NPRC A-55C in EH.
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