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In contrast, several hedgehog pathway genes and Foxa2 were more highly expressed on PNDl in the cervix/vagina compared with both the oviduct (Ihh, 11.0-fold; Dhh, 5.8-fold; Hhip, 42.1-fold; and Foxa2, 6.1-fold increased) and uterus (Ihh, 9.4-fold; Dhh, 6.2-fold; Hhipy 63.1-fold; and Foxa2, 651.7-fold increased), suggesting that these genes are also normally restricted to the posterior FRT.
Based on the findings from the GWAS of COPD in non-Asian populations, three top SNPs (rs1903003, rs2869967, and rs7671167) in FAM13a gene and five top SNPs (rs12504628, rs12509311, rs13118928, rs1512281, and rs1828591) in HHIP gene, which were found to be significantly associated with COPD risk, were selected [5-8] (the top SNP defined as P value was the most significant).
Linear regression analyses showed that three SNPs (rs12509311, rs13118928, and rs1828591) in the HHIP gene were significantly associated with the FEV1/FVC% in COPD with adjustment in combined population ([P.sub.max] = 4.1 x [10.sup.-4]) (Table 2).
GWAS have identified several susceptibility genes for COPD, including FAM13a, HHIP, CHRNA3/ CHRNA5/IREB2, RIN3, MMP3/MMP12, and TGFB2 [7, 8,10, 11,18-23].
It is biologically possible that HHIP may be involved in the etiology of COPD.
Furthermore, many previous studies have demonstrated significant genetic relationships between HHIP loci and the FEV1/FVC% such as in the GWAS of the Framingham Heart Study population , the Cohorts for Heart and Aging Research in Genomic Epidemiology and SpiroMeta consortia [5, 42], Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE), and International COPD Genetics Network (ICGN) subjects .
In conclusion, genetic variants in HHIP were found to be associated with the FEV1/FVC% in COPD cases.
Abbreviations COPD: Chronic obstructive pulmonary disease [FEV.sub.1]: Forced expiratory volume in 1 s FVC: Forced vital capacity FAM13a: Family with sequence similarity 13, member a HHIP: Hedgehog interacting protein GWAS: Genome-wide association study SNP: Single-nucleotide polymorphism.
Yang et al., "Association of HHIP polymorphisms with COPD and COPD-related phenotypes in a Chinese Han population," Gene, vol.
Lee et al., "Genetic variants in HHIP are associated with FEV1 in subjects with chronic obstructive pulmonary disease," Respirology, vol.
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