rs4522809

This functional study examined how genetic variants in SPP1 and TGFBR2 genes modulate osteopontin expression in Duchenne muscular dystrophy (DMD) muscle tissue. The SPP1 rs28357094 promoter variant (-66 G>T) did not significantly affect OPN expression levels in DMD patients (p=0.52), but TGFBR2 rs4522809 was a strong predictor of SPP1 mRNA expression (p=0.000001), with CC genotype showing highest expression and TT showing lowest. Lower OPN expression was independently associated with later age at loss of ambulation (RR=1.2, 95% CI 1.04-1.4, p=0.03), suggesting OPN as a disease severity modifier in DMD.

A pathway-wide association study in 425 case-parent triads examined 109 SNPs in 29 folate/one-carbon metabolism genes and 68 SNPs in 16 vitamin A metabolism genes for associations with cleft lip/palate (CL/P) and cleft palate only (CPO). Despite strong epidemiologic evidence that folic acid and vitamin A reduce cleft risk, no convincing genetic associations were found; the strongest association was FOLH1 with CPO (p=0.0008), but findings were fewer than expected by chance and inconsistent with protective effects of vitamin supplementation, suggesting vitamin metabolism gene polymorphisms do not play an etiologic role in oral facial clefts.