rs5918

This systematic review analyzed genetic associations with gastroschisis from 1980-2017, identifying 14 SNPs from 10 genes associated with crude risk and 30 SNPs from 14 genes with stratified risk. Four SNPs showed significant associations: rs4961 (ADD1, p=0.023), rs5443 (GNB3, p=0.002), rs1042713 (ADRB2, p=0.007), and rs1042714 (ADRB2, p=0.006). The findings suggest genetic susceptibility in gastroschisis is not restricted to gene-environment interactions, with blood pressure regulation genes playing a significant role in vascular disruption pathogenesis.

A candidate gene association study in 100 Russian vitiligo patients and 100 controls identified a strong novel association between GSTP1 rs1138272 (Ala114Val, OR=13.03, Bonferroni-adjusted P=0.0015) and vitiligo susceptibility. Cumulative analysis of multiple xenobiotic metabolizing genes showed that carrying higher numbers of risk alleles was associated with increased vitiligo risk (9-16 vs 3-8 alleles: OR=2.79, P=0.00063), supporting a polygenic model for vitiligo involving detoxification pathway genes.

Family-based association study of 290 Caucasian families investigating SLC6A4 and ITGB3 genes in autism, stratified by family history. While individual SNPs showed no significant associations after multiple testing correction, stratification by family history revealed nominally significant associations at rs2066713 (SLC6A4) in both positive and negative family history groups, and rs3809865 (ITGB3) in positive family history families. Gene-gene interaction analysis confirmed a significant interaction between rs2066713 (SLC6A4) and rs5918 (ITGB3, Leu33Pro) (p=0.014, survived multiple testing correction), suggesting family history is an important index of genetic heterogeneity in autism susceptibility.

This candidate gene association study examined 218 postmenopausal women at high breast cancer risk, testing 79 SNPs in steroid metabolism, receptor, cell cycle control, DNA repair, and carcinogen metabolism genes for associations with abnormal breast tissue cytomorphology (RPFNA atypia) as a biomarker for HRT-related breast cancer risk. Key findings: RAD54 Gln929Glu (rs3088074, OR=1.74), TFR Gly142Ser (rs3817672, OR=1.98, p=0.0025), VEGF 3'UTR (rs3025039, OR=2.12), and ACE I/D (rs4646994, OR=0.55) were associated with RPFNA atypia. RAD23B Ala249Val (rs1805329) showed strongest association with worsening cytomorphology on HRT versus off HRT (p=0.0009) and ERCC1 3'UTR (rs3212986) was borderline significant (p=0.0015). Results suggest DNA repair gene polymorphisms may modify breast tissue response to exogenous estrogens.

This association study examined epistatic interactions among seven serotonin pathway genes in autism etiology using 186 autistic families and 181 controls. The authors found a significant main effect of HTR5A rs1800883 (P = 0.0088), and identified a significant three-locus epistatic interaction between SLC6A4 intron 2 VNTR and ITGB3 rs5918 with additive HTR5A rs6320 effects (P < 0.001) associated with autism risk. Additionally, ITGB3 haplotypes showed association with platelet serotonin levels (P = 0.0163), supporting a common genetic mechanism linking gene interactions to both autism susceptibility and hyperserotonemia.

Family-based association study in 42 Antioquia families examining serotonergic gene variants and autism. Found significant associations with SLC6A4 variants rs4583306 (OR=2.6, p=0.004) and rs2066713 (OR=2.2, p=0.03), and evidence of epistasis between SLC6A4 and HTR2A (p<0.001) in autism etiology. The haplotype 5HTTLPR-rs4583306 (S-G) showed tripled autism risk (OR=3.4, p=0.01).