KISS-1 and GPR54 were regarded as key regulators for the puberty onset and fundamental gatekeepers of sexual maturation in mammals. To explore the possible association between variations in KISS-1 and GPR54 with sexual precocity, mutation screening of exon 1 of KISS-1 and exon 1, exon 3, and partial exon 5 of GPR54 was performed in a sexual precocious breed (Jining Grey goats) and sexual late-maturing breeds (Inner Mongolia Cashmere, Angora, and Boer goats) by PCR-SSCP. The results showed that five novel mutations were identified in exon 1 and partial exon 5 of GPR54 including C96 T, T173C, G176A, G825A, and C981 T. The Jining Grey goats with genotype BB or AB had 1.07 (P < 0.05) or 0.40 (P < 0.05) kids more than those with AA. The Jining Grey goats with genotype DD or CD had 1.80 (P < 0.05) or 0.55 (P < 0.05) kids more than CC, respectively. The present study preliminarily showed an association between alleles B and D of GPR54 with high litter size and sexual precocity in Jining Grey goats.

Summary Background Methotrexate (MTX) is an efficacious treatment for psoriasis; however, its widespread application is limited by its unpredictable efficacy. Objectives To investigate the association of clinical factors and variants of psoriasis susceptibility genes with clinical responses to MTX in a prospective cohort. Methods A total of 221 patients with psoriasis were recruited. Patients who achieved Psoriasis Area and Severity Index (PASI) improvement ≥ 75% at week 12 were defined as responders, whereas those with PASI improvement < 50% were defined as nonresponders. In 90 screening patients, genetic variants for 18 single‐nucleotide polymorphisms in 14 susceptibility genes, and HLA‐Cw6 status were initially compared for responders and nonresponders. Statistically significant associations in genetic variants were verified in all 221 patients. Results Overall, 49% and 45% of patients achieved PASI 75 improvement during screening and verification stages, respectively. Concomitant arthritis with psoriasis and high body mass index (BMI) negatively affect the efficacy of MTX. TT genotype of rs10036748 in TNIP1 was significantly associated with PASI 75 response at week 12 (54% and 37%, P < 0·05). A significantly higher PASI 90 response was observed in patients with TT genotype of rs10036748 (27% vs. 12%, P < 0·01) and TC/TT genotype of rs4112788 in LCE3D (25% vs. 13%, P < 0·05) at week 12 compared with those who had other genotypes. After adjustment for all confounding factors, only BMI (P < 0·05), arthritis (P < 0·05) and genotype of rs10036748 (P < 0·05) were significantly associated with clinical responses to MTX. Conclusions Patients with psoriasis with TT genotype of rs10036748 in TNIP1, with lower BMI, without arthritis will achieve a better response to MTX.

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