RESUMO
Genetic polymorphisms affect lipid profiles and are associated with disease complications. Genetic variants in the vitamin D receptor (VDR) gene are associated with type 2 diabetes mellitus (T2DM). In this study, we investigated the effects of VDR genotypes on the lipid profile and disease complications of T2DM patients in a Jordanian population. Ninety T2DM patients were genotyped for four major functional VDR genetic variants, rs2228570 C > T (FokI), rs7975232 A > C (ApaI), rs731236 T > C (TaqI), and rs1544410 C > T (BsmI), using the polymerase chain reaction−restriction fragment length polymorphism method. Lipid profiles and diabetes complications were analyzed and correlated with VDR genotypes. We found that the VDR rs7975232 and rs1544410 alleles were significantly (p = 0.008−0.04) associated with high-density lipoprotein (HDL) levels and retinopathy among patients. Carriers of the rs7975232 A/A genotype exhibited higher levels (49.68 ± 15.86 mg/dL) of HDL than patients with the A/C (44.73 ± 13.38 mg/dL) and C/C (37.93 ± 9.22 mg/dL) genotypes. Moreover, carriers of the rs1544410 T/T genotype had higher levels of HDL (54.31 ± 16.45 mg/dL) than patients with the C/T (43.57 ± 13.24 mg/dL) and C/C (43.98 ± 13.17 mg/dL) genotypes. T2DM patients who carry the rs7975232 C/C genotype were at higher risk (odds ratio [OR] = 7.88) of developing retinopathy compared with carriers of the rs7975232 C/A and A/A genotypes. In addition, T2DM patients with the rs1544410 C/C genotype had a higher risk (OR = 4.21) of developing retinopathy than patients with the rs1544410 C/T and T/T genotypes. Therefore, we concluded that the VDR rs7975232 and rs1544410 alleles were associated with HDL levels and retinopathy and can be considered as potential genetic biomarkers for the lipid profile and retinopathy complication among T2DM patients in a Jordanian population of Arabic origin. Further studies with larger sample sizes are needed to confirm our findings.
RESUMO
Breast cancer among Palestinian women has lower incidence than in Europe or North America, yet is very frequently familial. We studied genetic causes of this familial clustering in a consecutive hospital-based series of 875 Palestinian patients with invasive breast cancer, including 453 women with diagnosis by age 40, or with breast or ovarian cancer in a mother, sister, grandmother or aunt ("discovery series"); and 422 women diagnosed after age 40 and with negative family history ("older-onset sporadic patient series"). Genomic DNA from women in the discovery series was sequenced for all known breast cancer genes, revealing a pathogenic mutation in 13% (61/453) of patients. These mutations were screened in all patients and in 300 Palestinian female controls, revealing 1.0% (4/422) carriers among older, nonfamilial patients and two carriers among controls. The mutational spectrum was highly heterogeneous, including pathogenic mutations in 11 different genes: BRCA1, BRCA2, TP53, ATM, CHEK2, BARD1, BRIP1, PALB2, MRE11A, PTEN and XRCC2. BRCA1 carriers were significantly more likely than other patients to have triple negative tumors (p = 0.03). The single most frequent mutation was TP53 p.R181C, which was significantly enriched in the discovery series compared to controls (p = 0.01) and was responsible for 15% of breast cancers among young onset or familial patients. TP53 p.R181C predisposed specifically to breast cancer with incomplete penetrance, and not to other Li-Fraumeni cancers. Palestinian women with young onset or familial breast cancer and their families would benefit from genetic analysis and counseling.
