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India along with Nigeria and DRC contribute to 57% of the world sickle cell anemia population. The annual number of newborns in India with SCA was estimated at 44,000 in 2010. Even with this high prevalence there is minimal information about genetic factors that influence the disease course in Indian patients. The current study was conducted on 240 patients with SCD and 60 with sickle cell trait, to determine the association of genetic variants at the BCL11A (rs1427407) and HBS1-MYB (rs6934903) loci with fetal hemoglobin levels (HbF). Both these loci have been implicated with influencing HbF levels, a powerful modulator of the clinical and hematologic features of SCD. Our results indicate the BCL11A rs1427407 G > T variant to be significantly associated with HbF levels {19.12 ± 6.61 (GG), 20.27 ± 6.92 (GT) and 24.83 ± 2.92 (TT) respectively} contributing to ~ 23% of the trait variance. Interestingly no association of the HBS1L-MYB rs6934903 with the HbF levels was seen. The present study indicates the BCL11A (rs1427407) but not HMIP (rs6934903) to be associated with elevated HbF levels in Indian patient. Further interrogation of additional variants at both the loci; as also a GWAS which may help uncover new loci controlling HbF levels. [ABSTRACT FROM AUTHOR]

Background : Fetal hemoglobin (HbF) levels in sickle cell anemia patients vary. We genotyped polymorphisms in the erythroid-specific enhancer of BCL11A to see if they might account for the very high HbF associated with the Arab–Indian (AI) haplotype and Benin haplotype of sickle cell anemia. Methods and results : Six BCL112A enhancer SNPs and their haplotypes were studied in Saudi Arabs from the Eastern Province and Indian patients with AI haplotype (HbF ~ 20%), African Americans (HbF ~ 7%), and Saudi Arabs from the Southwestern Province (HbF ~ 12%). Four SNPs (rs1427407, rs6706648, rs6738440, and rs7606173) and their haplotypes were consistently associated with HbF levels. The distributions of haplotypes differ in the 3 cohorts but not their genetic effects: the haplotype TCAG was associated with the lowest HbF level and the haplotype GTAC was associated with the highest HbF level and differences in HbF levels between carriers of these haplotypes in all cohorts were approximately 6%. Conclusions : Common HbF BCL11A enhancer haplotypes in patients with African origin and AI sickle cell anemia have similar effects on HbF but they do not explain their differences in HbF. [ABSTRACT FROM AUTHOR]

Abstract: Background: Bone morphogenetic protein (BMP) are involved in the various orthopedic complications such as avascular necrosis, osteonecrosis and bone turnover, therefore genes coding for proteins, like BMP4, can be potential candidate for studying orthopedic disorders. Methods: A case–control study was conducted to examine the association between SNP T538C of BMP4 and orthopedic complications in sickling patients by employing PCR-RFLP. Results: A total of 200 cases and 172 control groups were studied from Indian population. T538C SNP has not been implicated in disease and doesn''t increase the risk (OR=0.89, OR=0.68). We observed no significant association between the T538C polymorphism and case group in the studied population. However, we observed significantly increased uric acid and LDH level in homowild (TT), heteromutant (TC) and homomutant (CC) in case group compared to control group ( all p =0.0001) and (p =0.0001, p =0.0001, p =0.015 and p =0.0001, p =0.0001, p =0.0001 respectively) in the studied population. Conclusions: The T/C polymorphism in BMP4 is not associated with case group and in view of present observation, we suggest that evaluation of LDH and uric acid level and its association with polymorphisms in the BMP4 may be considered to be reliable molecular and biochemical markers, and possess promising rational for diagnostic potential in clinical cases. [Copyright &y& Elsevier]