Over-Representation of Recessive Osteogenesis Imperfecta in Asian Indian Children

Several genes are implicated in the etiology of early onset osteogenesis imperfecta (OI). The various genes causing severe OI include WNT1, SERPINF1, P3H1, CREB3L1, and CRTAP, although glycine substitutions in COL1A1chains have also been predicted to cause perinatal lethal OI . Patients with early onset OI present decreased mobility, recurrent rib fractures, bony deformities, and chest infections that lead to an early death. We report our experience in children with OI in Asian Indian families, which includes two patients with SERPINF1 pathogenic variants; and another two patients with severe OI and antenatal fractures caused by pathogenic variants in the CRTAP gene, identified by next generation sequencing (NGS). For one affected fetus, medical termination of pregnancy was done. The other baby was started on zoledronate therapy just after birth and is now 3 years old. Prenatal diagnosis was subsequently done on chorionic villus sample in the latter family.

Polymorphisms in the IL6 gene in Asian Indian families with premature coronary artery disease – The Indian Atherosclerosis Research Study

SummaryInflammation plays a major role in coronary artery disease (CAD). We investigated the polymorphisms in the interleukin 6 (IL6) gene and their effect on the expression of acute-phase proteins in premature CAD in Asian Indian families. One hundred and ninety affected sibling pairs (ASPs) were genotyped for three tag single nucleotide polymorphisms (SNPs) in the IL6 gene for linkage analysis. We observed suggestive logarithm of odds (LOD) score for one SNP (rs2066992) in a subset of 62 ASPs with the age at onset less than 45 years (LOD score = 1.114, p = 0.011 in linkage analysis; pi = 0.55, p = 0.008 in identity by descent; LOD score = 1.06, p = 0.014 in quantitative trait locus for plasma levels of high sensitivity C-reactive protein, hsCRP). This was followed by sequencing of the promoter region and haplotype analysis in 46 probands and 40 controls. Five out of the eight previously reported promoter SNPs were found to be polymorphic (rs1800797, rs1800796, rs7802307, rs7802308, rs1800795). Two novel sequence variants were also found. One promoter haplotype (GGAAG) was detected with an odds ratio (OR) of 3.676 (p = 0.0017, 95% confidence interval [CI]: 1.68 – 8.045) and population attributable risk of 21.1% (95%CI: 9.2%-31.5%). The plasma levels of both hsCRP and fibrinogen exhibited significant association with these promoter SNP genotypes (p < 0.001). In conclusion, IL6 gene polymorphisms appear to be important genetic factors in premature CAD, and in the regulation of key atherogenic markers in Asian Indian families.