Are COL4A1 and COL4A2 gene polymorphisms associated with cerebral palsy?

OBJECTIVES: This study aims to investigate the association of COL4A1 and COL4A2 gene polymorphisms with susceptibility to risk of developing cerebral palsy (CP) and severity of CP. PATIENTS AND METHODS: Between December 2016 and June 2017, a total of 176 patients with CP (101 males, 75 females; mean age 71.8±37.9 months; range, 24 to 184 months) and age-, sex-, and ethnically-matched 178 (90 males, 88 females; mean age 69.3±55.2 months; range, 24 to 214 months) controls were included. Two polymorphisms of COL4A1 (rs1961495) and COL4A2 (rs9521733) genes were typed from genomic deoxyribonucleic acid. Genotype distributions and allelic frequencies were compared between the patient and control groups. Gross Motor Function Classification System, the use of medical drugs, type of involvement, number of affected limbs, accompanying conditions, birth weight, gestational age, and magnetic resonance imaging (MRI) findings were used to evaluate the disease severity and their relationships with the COL4A1 and COL4A2 gene polymorphisms. RESULTS: There was no statistically significant difference between the groups in terms of genotype distribution and allele frequency of COL4A1 and COL4A2 gene polymorphisms (p>0.05). In addition, there was no relationship between severity of CP and two gene polymorphisms (p>0.05). A significant association was detected between the COL4A2 polymorphism and growth retardation in CP. The TT genotype (57.1%) and T allele (76.2%) were higher, compared to CC (4.8%) and CT genotypes (38.1%) and C allele (23.8%) in patients with CP with growth retardation (p=0.03 for genotype and p=0.01 for allele frequency). CONCLUSION: These findings suggest that COL4A1 and COL4A2 gene polymorphisms are not associated with susceptibility to CP in a group of Turkish populations, although COL4A2 gene polymorphism may be associated with growth retardation in patients with CP.

Harnessing Knowledge on Very Important Pharmacogenes CYP2C9 and CYP2C19 Variation for Precision Medicine in Resource-Limited Global Conflict Zones.

Pharmacogenomics harnesses the utility of a patient's genome (n = 1) in decisions on which therapeutic drugs and in what amounts should be administered. Often, patients with shared ancestry present with comparable genetic profiles that predict drug response. However, populations are not static, thus, often, population mobility through migration, especially enmasse as is seen for refugees, changes the pharmacogenetic profiles of resultant populations and therefore observed responses to commonly used therapeutic drugs. For example, in the aftermath of the Syrian civil war since 2011, millions have fled their homes to neighboring countries in the Middle East. The growing permanence of refugees and mass migrations is a call to shift our focus in the life sciences community from old models of pharmaceutical innovation. These seismic social changes demand faster decisions for "population-to-population bridging," whereby novel drugs developed in or for particular regions/countries can meet with rational regulatory decisions/approval in world regions impacted by migrant/refugee populations whose profiles are dynamic, such as in the Eastern Mediterranean region at present. Thus, it is important to characterize and report on the prevalence of pharmacogenes that affect commonly used medications and predict if population changes may call for attention to particular differences that may impact health of patients. Thus, we report here on four single-nucleotide polymorphism (SNP) variations in CYP2C9 and CYP2C19 genes among Mersin-Turkish healthy volunteers in the Mersin Province in the Eastern Mediterranean region that is currently hosting a vast number of migrant populations from Syria. Both CYP2C9 and CYP2C19 are very important pharmacogene molecular targets. We compare and report here on the observed SNP genetic variation in our sample with data on 12 world populations from dbSNP and discuss the feasibility of forecasting the pharmacokinetics of drugs utilized by migrant communities in Mersin and the Eastern Mediterranean region. This study can serve as a catalyst to invest in research in Syrian populations currently living in the Eastern Mediterranean. The findings have salience for rapid and rational regulatory decision-making for worldwide precision medicine and, specifically, "pharmacogenovigilance-guided bridging of pharmacokinetics" across world populations in the current era of planetary scale migration.

Relation of the Fas and FasL gene polymorphisms with susceptibility to and severity of rheumatoid arthritis.

To investigate associations of the Fas and FasL genes polymorphisms with rheumatoid arthritis (RA). One hundred patients with RA and age-, sex- and ethnically matched 101 controls were included. Four polymorphisms of Fas (-670 A>G rs1800682, -1377 G>A rs2234767) and FasL (IVS2nt-124 A>G rs5030772, -844 T>C rs763110) genes were typed from genomic DNA. Genotype distributions and allelic frequencies were compared between patients and control subjects. After the history and clinical examination of patients with RA, in terms of pain, fatigue and general health status were evaluated by visual analogue scale. Thereafter, erythrocyte sedimentation rate, C-reactive protein, blood count and rheumatoid factor levels were measured. The Disease Activity Score-28, Health Assessment Questionnaire and modified Sharp score were used to evaluate the disease activity, functional disability and radiological damage, and their relationships with the Fas and FasL gene polymorphisms were investigated. In patients with RA, CT and TT genotypes of FasL-844, polymorphism were twofold and 4.8-fold higher, and AA genotype of FasL IVS2nt-124 polymorphism was 3.4-fold higher than the control group (respectively, p = 0.05, p = 0.002, p = 0.039). T allele of FasL-844 polymorphism was more frequent in patients than controls (respectively, 52.5 vs. 41.4 %, p = 0.027). Any association was not detected between Fas (-670 A>G, -1377 G>A) and FasL (-844 T>C, IVS2nt-124 A>G) gene polymorphisms with the disease activity scores, functional disability and radiological damage. However, the Fas-670 A>G polymorphism was associated with drug therapy (p = 0.049). The distribution of GG genotype was higher compared to GA or AA genotypes in patients using triple disease-modifying antirheumatic drug therapy (71.4, 14.3 and 14.3 %, respectively). These findings suggest that the -844 T>C and IVS2nt-124 A>G polymorphisms in the FasL gene related with apoptosis may increase genetic susceptibility to RA in a Turkish population. In addition, the Fas-670 A>G gene polymorphism may be associated with disease progression. There is a need for further studies to clarify the genetic role of apoptosis in RA.

Apoptosis-related Fas and FasL gene polymorphisms' associations with knee osteoarthritis.

To investigate the associations between Fas and FasL gene polymorphisms and susceptibility to knee osteoarthritis. Genomic DNA was obtained from 146 patients with knee osteoarthritis and 102 healthy controls. Genotype distributions and allelic frequencies of four polymorphisms of Fas (-670 G>A rs1800682, -1377 G>A rs2234767) and FasL (IVS2nt-124 A>G rs5030772, -844 T>C rs763110) genes were compared between the groups. Thereafter, this association was investigated between patients and controls of the same sex. There were significant differences between patients with knee osteoarthritis and controls regarding the genotype distributions and allelic frequencies of Fas-1377 G>A polymorphism (P = 0.0001 and P = 0.005, respectively). The Fas-1377 GG genotype and G allele were significantly more frequent in patients with knee osteoarthritis than in controls. Genotype distributions and allelic frequencies of Fas-670 G>A, FasL-844 T>C, and FasL IVS2nt-124 A>G polymorphisms did not differ between the groups (P > 0.05). However, there were no significant differences between patients and controls of the same sex (P > 0.05). These findings suggest that the Fas-1377 G>A polymorphism in the Fas gene related with apoptosis may contribute to susceptibility to knee osteoarthritis in the Turkish population. There is a need for further studies to evaluate the role of apoptosis in large cohorts.

Which genotype of MAO gene that the patients have are likely to be most susceptible to the symptoms of fibromyalgia?

The objective of this study was to analyze the genotype distributions and allele frequencies for the MAO-A and MAO-B polymorphism of the MAO gene among the patients with fibromyalgia syndrome (FS). One hundred and seven fibromyalgia patients and 90 unrelated healthy subjects were included into the study. Genomic DNA of 107 FS patients and 90 healthy control subjects were analyzed by polymerase chain reaction. Polymorphism of the MAO gene was: 1-1, 1-3, 3-3, 3-4. The "allele 3" had a 2.7 to 4.8-fold increased transcription activity than the "allele 1". The frequencies of the genotypes of the patients with FS and healthy controls were compared. Although no significant difference was found in genotypes of patients and controls (P = 0.0559), it is likely that "allele 3" could be a more riskful factor for FS than "allele 1" (P = 0.033). Fibromyalgia impact questionnaire was administered to FS group as well as control group. One of our findings is that, the patients whose genotype 3-3 may be mostly affected by the symptoms of FS. In conclusion, it seems plausible to say that MAOA-dependent metabolism of the biological amines may be partly related to high-activated MAO-A, allele 3, in the occurrence of FS among Turkish population.