Figure 1 - uploaded by Miguel A. Alfonso-Sanchez
Content may be subject to copyright.
Hierarchical phylogenetic relationships of Y-chromosome haplogroups and their percentages in Sousse.
Source publication
The male genetic landscape of the territory currently known as Tunisia is hampered by the scarcity of data, especially from cosmopolitan areas such as the coastal city of Sousse. In order to alleviate this lacuna, 220 males from Sousse were examined, for the first time, for more than 50 Y-chromosome single-nucleotide polymorphisms (Y-SNPs) markers...
Contexts in source publication
Context 1
... phylogenetic relationship of these markers and the haplogroups that they define are indicated in Figure 1. The Y-SNP haplogroup nomenclature follows the recommendation originally proposed by Karafet et al. 25 and revised by additional lineage information as established by subsequent scientific teams. ...
Context 2
... Statistical analyses A total of 23 key geographically targeted reference populations previously typed for both Y-STR and Y-SNP markers and published were utilized for the phylogenetic analyses (Supplementary Table S1). They correspond to 17 countries in North Africa, the Near East and Europe as well as some sub- Saharan African countries (Supplementary Figure S1). ...
Context 3
... prevent the Kriging interpolation from performing unrealistic gradient estimation, boundaries of large uninhabitable areas were defined. (See Supplementary Figure S1 for the location of the observed values). Phylogenetic relationships among the microsatellite haplotypes belonging to haplogroups E-M81, E-M78, J-M267, J-M172 and R-M207 were inferred through median joining networks using the NETWORK 4.6.0.0 (Fluxus Engineering, Suffolk, UK) 28 and Network Publisher version 1.2.0.0 (Fluxus Engineering, www.fluxusengineering.com) ...
Context 4
... partitioning of paternal lineages and their frequencies are displayed in a hierarchical phylogeny in Figure 1. The 220 Sousse Y-chromosomes represent 24 different haplogroups, the majority of them belonging to haplogroups E and J that account for 90% of our dataset (E; 56% and J; 34%) (Supplementary Table S3). ...
Context 5
... phylogenetic relationship of these markers and the haplogroups that they define are indicated in Figure 1. The Y-SNP haplogroup nomenclature follows the recommendation originally proposed by Karafet et al. 25 and revised by additional lineage information as established by subsequent scientific teams. 26,27 Statistical analyses A total of 23 key geographically targeted reference populations previously typed for both Y-STR and Y-SNP markers and published were utilized for the phylogenetic analyses (Supplementary Table S1). They correspond to 17 countries in North Africa, the Near East and Europe as well as some sub- Saharan African countries (Supplementary Figure ...
Context 6
... phylogenetic relationship of these markers and the haplogroups that they define are indicated in Figure 1. The Y-SNP haplogroup nomenclature follows the recommendation originally proposed by Karafet et al. 25 and revised by additional lineage information as established by subsequent scientific teams. 26,27 Statistical analyses A total of 23 key geographically targeted reference populations previously typed for both Y-STR and Y-SNP markers and published were utilized for the phylogenetic analyses (Supplementary Table S1). They correspond to 17 countries in North Africa, the Near East and Europe as well as some sub- Saharan African countries (Supplementary Figure ...
Context 7
... distribution maps for haplogroups (contour map) were obtained using the Surfer v8.07 software (Golden Software, Golden, CO, USA, http:// www.goldensoftware.com). Previously published data on African and Arabian populations were included to build the grid (Supplementary Table S2). We employed the ordinary Kriging procedure with default settings for interpolating frequency values. Kriging variance was used to compute the confidence interval limits of the estimated values. Kriged values falling out of the confidence interval limits were not considered in the analyses. To prevent the Kriging interpolation from performing unrealistic gradient estimation, boundaries of large uninhabitable areas were defined. (See Supplementary Figure S1 for the location of the observed values). Phylogenetic relationships among the microsatellite haplotypes belonging to haplogroups E-M81, E-M78, J-M267, J-M172 and R-M207 were inferred through median joining networks using the NETWORK 4.6.0.0 (Fluxus Engineering, Suffolk, UK) 28 and Network Publisher version 1.2.0.0 (Fluxus Engineering, www.fluxusengineering.com) softwares, using weighting based on the inverse of the microsatellite variances. The networks generated are based on the following 10 Y-STR loci: DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438 and DYS439. These loci are in common among all relevant reference populations (Supplementary Table S2) included in the analyses. DYS385 a/b were excluded from the analyses since the multiplex amplification reactions do not allow for the discrimination between the two loci. DYS389II was scored by subtracting the DYS389I allele from the total fragment. 29 Times to the most common recent ancestor for the most diagnostic Y haplogroups were estimated by calculating the mean STR variance as proposed by Kayser et al. 30 using a mean STR mutation rate of 0.000 69 per generation of 25 years. 31 ...
Context 8
... partitioning of paternal lineages and their frequencies are displayed in a hierarchical phylogeny in Figure 1. The 220 Sousse Y-chromosomes represent 24 different haplogroups, the majority of them belonging to haplogroups E and J that account for 90% of our dataset (E; 56% and J; 34%) (Supplementary Table S3). The predominant E sublineage, also commonly found in other North African populations, 18-22 is E-M81. All E-M81 derived chromosome are in subhaplogroup E-M183 (44.55%). Besides the common E-M81 lineage, traces of other lineages within the major E-M215 haplogroup were detected including E-M35, E-M78 and E-M123. These lineages are also found at various frequencies throughout North and East Africa. Haplogroup E-M78 which has a wide distribution, including Europe, the Near East and North Africa, 20 is mostly represented by subhaplogroup E-V65 (4.09%), with the exception of two individuals that belong to subhaplogroups E-V13 and E-V22 (0.45% each). Lineage E-M123, on the other hand, is detected at low frequency (1.82%). It is interesting that the E-M2 clade which is particularly frequent in sub-Saharan Africa 33,34 and present in some North African populations most likely as a result of sub-Saharan migration 18,19,35 , is not detected in the Sousse samples. The second most prevalent major lineage detected in our dataset is J-M304 encompassing 34% of the total male population. Both of its main branches, J-P58 and J-M172, were observed. Haplogroup J-P58, which is thought to have originated in eastern Anatolia, 36 is largely represented by subhaplogroup J-L- -222.2 (23.64%). Within the J-M172 clade, the majority of males are represented by the J-L24 subclade (5.45%). Furthermore, Y-hap- logroup R-M207 is found in 12 Sousse males of which three individuals are either R-M198 (0.45%) or R-V88 (0.91%). Also present were haplogroups G-M201, L-L20, T-M184 and A-M91, although each of these accounted for only 0.45% of the entire sample ...
Similar publications
The demographic history of human populations in North Africa has been characterized by complex processes of admixture and isolation that have modeled its current gene pool. Diverse genetic ancestral components with different origins (autochthonous, European, Middle Eastern, and sub-Saharan) and genetic heterogeneity in the region have been describe...
Citations
... This study was conducted on 246 Tunisian patients who originated from the Sahel region. This discrepancy could be due to Tunisian high genetic heterogeneity 30,54,55 . Thus, the T allele follows a south/north gradient from Africa to Europe, via Tunisia. ...
Adverse drug reactions (ADR) represent a significant contributor to morbidity and mortality, imposing a substantial financial burden. Genetic ancestry plays a crucial role in drug response. The aim of this study is to characterize the genetic variability of selected pharmacogenes involved with ADR in Tunisians and Italians, with a comparative analysis against global populations. A cohort of 135 healthy Tunisians and 737 Italians were genotyped using a SNP array. Variants located in 25 Very Important Pharmacogenes implicated in ADR were extracted from the genotyping data. Distribution analysis of common variants in Tunisian and Italian populations in comparison to 24 publicly available worldwide populations was performed using PLINK and R software. Results from Principle Component and ADMIXTURE analyses showed a high genetic similarity among Mediterranean populations, distinguishing them from Sub-Saharan African and Asian populations. The Fst comparative analysis identified 27 variants exhibiting significant differentiation between the studied populations. Among these variants, four SNPs rs622342, rs3846662, rs7294, rs5215 located in S LC22A1 , HMGCR, VKORC1 and KCNJ11 genes respectively, are reported to be associated with ethnic variability in drug responses. In conclusion, correlating the frequencies of genotype risk variants with their associated ADRs would enhance drug outcomes and the implementation of personalized medicine in the studied populations.
... Structure analysis. The structure of 38 Middle Eastern [18][19][20][21][22][23][24][25][26][27][28][29][30] and 97 African populations [28,[38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] was investigated using the programme STRUCTURE version 2.3.7 and an admixture model [13,57]. The graph of population Q-matrix was created using Y-STR data from 17 markers across 135 populations (11,305 individuals). ...
The Y-chromosome has been widely used in forensic genetic applications and human population genetic studies due to its uniparental origins. A large database on the Qatari population was created for comparison with other databases from the Arabian Peninsula, the Middle East, and Africa. We provide a study of 23 Y-STR loci included in PowerPlex Y23 (Promega, USA) that were genotyped to produce haplotypes in 379 unrelated males from Qatar, a country at the crossroads of migration patterns. Overall, the most polymorphic locus provided by the Promega kit was DYS458, with a genetic diversity value of 0.85 and a haplotype diversity of 0.998924. Athey's Haplogroup Predictor tool was used to predict haplogroups from Y-STR haplotypes in the Qatari population. In a median-joining network, the haplogroup J1 predominance (49%) in Qatar generated a star-like expansion cluster. The graph of population Q-matrix was developed using Y-STR data from 38 Middle Eastern and 97 African populations (11,305 individuals), and it demonstrated a stronger sub-grouping of countries within each ethnic group and showed the effect of Arabs on the indigenous Berbers of North Africa. The estimated migration rate between the Qatari and other Arabian populations was inferred using Bayesian coalescence theory in the Migrate-n program. According to the Gene Flow study, the main migration route was from Yemen to Kuwait through Qatar. Our research, using the PowerPlex Y23 database, shows the importance of gene diversity, as well as regional and social structuring, in determining the utility of demographic and forensic databases.
... These results indicate that the genetic relationships among the 16 populations are related to their geographic distribution. Our results agree with prior analyses of uniparental Y-chromosome markers, which were conducted on the population of Sousse by Fadhlaoui-Zid et al. (2015). This analysis indicates a distinctive North-African cluster that separates from the rest of the Sub-Saharan Africa and Western Europe. ...
Background:
Tunisia has a complex demographic history of migrations from within Africa, Europe, and the Middle East. However, only one population study based on X-STR markers has been reported so far.
Aim:
To investigate the genetic polymorphisms of 17 X-STRs in two Tunisian populations from the cities of Sousse and Makthar, and to reveal the genetic relationships with other reference populations.
Subjects and methods:
A total of 194 unrelated healthy individuals were analysed for seventeen X-STR markers.
Results:
Our results indicate that DXS6809 is the most polymorphic locus, whereas DXS6807 is the least informative marker in the populations of Sousse and Makthar. In addition, forensic statistical parameters, such as the power of discrimination in males and females, as well as the mean of exclusion in duos and trios, reveal that the panel of 17 X-STRs is highly informative and useful in different forensic applications. Overall, pairwise genetic distances (Fst) and non-metric MDS plots demonstrate clustering of different populations according to their geographic locations and their historical relationships.
Conclusion:
Overall, the study of X-STR markers of the Tunisian populations can help to promote the establishment of a forensic DNA reference database in Tunisia and provide reference for future anthropological research.
... Among them, the studied population, sample size, environmental factors, dietary conditions and life style. Moreover, the heterogeneous genetic structure of some studied populations [45] could also be considered as a crucial factor explaining the difference in genetic susceptibility to NPC and, therefore, these overall contradictory findings described in genetic association studies. In the present study, we also found that the genotype distribution of GPx-1 Pro198Leu variant according to clinicopathological characteristics of NPC patients had no significant association with age, gender, tumor size, lymph node status, metastasis and stage. ...
PurposeGlutathione peroxidase 1 (GPx-1) is a selenium-dependent detoxifying enzyme involved in the protection of cells against oxidative damage. Some genetic association studies reported significant associations between GPx-1 Pro198Leu variant and carcinogenesis across different populations; however, the impact of this variant on nasopharyngeal carcinoma (NPC) has not been explored. Therefore, the present study was planned to evaluate the potential involvement of the GPx-1 Pro198Leu variant and plasma GPx activity in the risk of developing NPC in a Tunisian population.Methods
The GPx-1 Pro198Leu genotype was determined in 327 NPC patients and 150 healthy controls by the RFLP-PCR analysis. The correlation between the GPx-1 variant and the clinicopathological parameters was examined. GPx activity was assessed in the plasma of 119 NPC patients and 58 healthy control subjects and according to GPx-1 genotypes and clinicopathological characteristics of NPC patients.ResultsA significant association was found between GPx-1 Pro198Leu variant and NPC risk in a Tunisian population. The allelic frequencies of Pro and Leu alleles were 32% versus 68% and 41% versus 59% in NPC cases and controls, respectively. Thus, the minor 198 Leu allele increased significantly in NPC patients and appeared as a potential risk factor for NPC occurrence (OR = 1.48, CI 95% = 1.14–1.91, p = 0.002). The plasma GPx activity was significantly higher in NPC patients than in controls (p = 0.03). According to the clinicopathological characteristics of NPC patients, GPx activity decreased significantly in patients with lymph node metastasis (p = 0.004).Conclusion
This is the first study showing a strong association between GPx-1 Pro198Leu genetic variant and NPC risk. GPx-1 Pro198Leu variant increased the development of regional lymph node metastasis. Plasma GPx activity was higher in NPC patients. Thus, GPx-1 gene could be considered as a determinant factor influencing NPC risk and progression.
... Then, using a resolution of 12 Y-STR loci, those typed in all populations, we performed MDS based on pairwise R ST genetic distances (Fig. 2) that showed a sharp geographical clustering separating Sub-Saharan, European, and Middle Eastern populations in the negative part of dimension 1 from most of North African populations, including Tunisian ones, in the positive part of that dimension. The proximity of Sub-Saharan populations closer to European than to North African ones is in accordance with previous studies14,22,45,46 and the outsider positions of the Kenyans and the Finnish just reflect the peculiarities of these two populations, since the Kenyans considered were Maasai, among whom a considerable degree of endogamy has been reported and the Finnish are known to have passed through a recent bottleneck46 .Not devaluating the overrepresentation of Tunisians in this analysis, is of note the diversity of Tunisian populations: the Tunisian Berbers are very dispersed, denoting well their heterogeneity; the Cosmopolitans and Tunisian Andalusians are more central in the plot close to the non-Tunisian North Africans; and the two studiedArab populations are rather apart from each other, with Kairouan near Berber populations and Wesletia showing more affinities with Middle Eastern ones. Within the North African populations, the Egyptian reveals the closest similarities with Middle Eastern ones. ...
To obtain refreshed insights into the paternal lineages of Tunisian populations, Y-chromosome diversity was assessed in two populations belonging to an Arab genealogical lineage, Kairouan and Wesletia, as well as in four Tunisian Andalusian populations, Testour, Slouguia, Qalaat-El-Andalous and El Alia. The Arabs from Kairouan revealed 73.47% of E-M81 and close affinities with Berber groups, indicating they are likely arabized Berbers, clearly differentiated from the Arabs from Wesletia, who harbored the highest frequency (71.8%) of the Middle Eastern component ever observed in North Africa. In the Tunisian Andalusians, the North African component largely prevailed, followed by the Middle Eastern contribution. Global comparative analysis highlighted the heterogeneity of Tunisian populations, among which, as a whole, dominated a set of lineages ascribed to be of autochthonous Berber origin (71.67%), beside a component of essentially Middle Eastern extraction (18.35%), and signatures of Sub-Saharan (5.2%), European (3.45%) and Asiatic (1.33%) contributions. The remarkable frequency of T-M70 in Wesletia (17.4%) prompted to refine its phylogeographic analysis, allowing to confirm its Middle Eastern origin, though signs of local evolution in Northern Africa were also detected. Evidence was clear on the ancient introduction of T lineages into the region, probably since Neolithic times associated to spread of agriculture.
... Sample sizes, ethnic heterogeneity and environmental factors may contribute to these contradictory findings. Moreover, it has been clearly reported that the Tunisian population is a mixture of many cultures and showed a very heterogeneous genetic structure [16], which could explain the difference in genetic susceptibility to NPC. In contrast to NOS3 G894T variant, our study showed no significant association between NOS3 T-786C The association studies between NOS3 T-786C promoter variant and cancer risk showed conflicting results. ...
Purpose
We conduct this study to evaluate the clinical and functional impact of Nitric Oxide Synthase 3 (NOS3) T-786C and G894T genetic variants on nasopharyngeal carcinoma (NPC) risk and progression in a Tunisian population.
Methods
259 NPC patients and 169 healthy controls were enrolled into our case–control study. Blood samples were genotyped by the RFLP-PCR analysis. The levels of Nitric oxide (NO) were measured by a colorimetric assay kit in the plasma of NPC patients, healthy controls and according to NOS3 genotypes. The correlation between the NOS3 variants and the clinicopathological parameters was examined.
Results
We found no linkage disequilibrium between NOS3 T-786C and G894T variants. These results showed that NOS3 variants were genetically independent. In contrast to NOS3 T-786C, a significant association was found between NOS3 G894T polymorphism and NPC risk. The 894T allele decreased significantly in NPC patients and appeared as protective factor (OR = 0.65, CI 95%= 0.48–0.88, p = 0.006). NPC patients had significantly higher levels of plasma NO as compared to healthy controls (p = 0.0011). The T-786C mutation reduced the levels of plasma NO and decreased risk of lymph node metastasis in NPC patients (OR = 0.64, 95% CI = 0.43–0.96; p = 0.03). In contrast, NOS3 G894T polymorphism had no effects neither on NO plasma levels nor clinical parameters.
Conclusions
This is the first study to associate NPC with significantly higher levels of plasma NO. NOS3-derived NO could play key roles in NPC pathogenesis. NOS3 variants differently contribute to NPC risk and progression in a Tunisian population. NOS3 G894T was associated with NPC risk. NOS3 T-786C decreased the levels of plasma NO and reduced the development of regional lymph node metastasis.
... Within the cluster of North African populations the Sousse population sample is somewhat different from the other six populations. One has to analyze more in depth the reasons of this isolation that has been shown by other genetic studies (Fadhlaoui-Zid et al., 2015). It seems that the particular genetic structure of Sousse would be more related to the high level of admixture of this ...
... Indeed, this city is from an ancient foundation by Phoenicians 1100 years BC, Interestingly, it is one of the rare Punic towns that escaped destruction by Romans during the Punic wars. The presence of the Phoenician Y chromosome at a frequency of about 10% in Sousse (Fadhlaoui-Zid et al., 2012;Fadhlaoui-Zid et al., 2015) confirms the continuity of this population since its foundation. Moreover its location on the sea and its economic role leading to commercial and human exchanges would explain the diversity observed at haplotypic level. ...
The COMT gene encodes for catechol-O-methyl-transferase, an enzyme playing a major role in regulation of synaptic catecholamine neurotransmitters. Investigating 4 markers of the COMT gene (rs2020917, rs4818, rs4680, rs9332377) in 6 Tunisian populations and a pool of Libyans. Our objective was to determine the distribution of allelic, genotypic and haplotypic frequencies by comparison to other populations of the 1000 genomes project and 59 populations from the Kidd Lab dataset. The allelic frequencies established for these SNPs in the North African populations are similar to those of Europeans and South Asians. Linkage disequilibrium between these SNPs and haplotypes frequencies are different between populations whose clustering in principal components analysis (PCA) according to their geographic origin was more significant using haplotypic frequencies. COMT activity prediction by haplotypes genotyping could be limited to rs4818-rs4680 micro-haplotypes. The Low activity haplotype (CG) displays the highest frequency in African populations (55%), in the 59 Kidd Lab populations we found also that Sub-Saharan Africans, Native Americans, and some East Asian and Pacific Island populations all have frequencies in the 50–81% range for (CG) where as its lowest frequency was found in Europeans (10%), this results have been also confirmed for Southwest Asians. North Africans and South Asians with intermediate frequencies have approximately similar values (20% and 25%). Europeans show the highest frequencies of haplotypes with predicted High and Medium activity in contrast to Africans. North Africans and South Asians present similar results for all the category of the COMT activity prediction by haplotypes genotyping. The high level of genetic diversity of COMT haplotypes, not only allows distinction between populations according to their history settlement, origin and ethnicity, it constitutes a basis for studies of association of the COMT gene polymorphism with pathologies, drugs response and for forensic investigation in North African populations.
... In this regard Africa, despite being the continent with the greatest genetic diversity, is very poorly represented when, for instance, 90% of some clinically relevant polymorphisms of cytochrome P450 enzymes show prevalences of up to 24% in African populations (Alessandrini et al. 2013;Beltrame et al. 2016). This scarcity of data is even more pronounced for North African populations, whose genetic background can be summarised as autochthonous Maghrebi or Berber with differential Middle Eastern, European, and Sub-Saharan African contributions (Gonz alez-P erez et al. 2010;Cherni et al. 2011;Henn et al. 2012;Bekada et al. 2015;Fadhlaoui-Zid et al. 2015). The complex genetic background of North African populations, together with some cultural behaviours such as the high proportion of consanguineous marriages, make these populations particularly interesting in terms of medical genetics, personalised medicine, and pharmacogenomics (Belhassan et al. 2016). ...
... North African populations are genetically rich and heterogenous, as many papers have outlined, through analysing autosomal and uniparental data (Gonz alez-P erez et al. 2010; Henn et al. 2012;Bekada et al. 2015;Fadhlaoui-Zid et al. 2015). This genetic richness goes beyond the ethnic differences among countries or within Berber and Arab cultures. ...
Background: Genetic variation in glucuronosyltransferases (UGT) is crucial in drug metabolism and risk of some diseases
Aim: To examine genetic variation in glucuronosyltransferases (UGT)in North African populations. Subjects & Methods: Allele frequencies of SNPs UGT1A424Thr, UGT1A448Val, UGT2B1585Tyr, UGT2B15523Thr and UGT2B17 CNV deletion from Morocco, Algeria, Tunisia and Libya were compared to European and Sub-Saharan populations. Results: North Africans are the group with the highest genetic heterogeneity given by internal differences in the occurrence of UGT2B17 deletion, UGT1A448Val and UGT1A4 haplotypes. UGT2B15 SNPs differentiate Sub-Saharans from the rest of populations. Conclusion: North African populations show high frequency of carriers of UGT2B15523Thr, a variant linked to an increased risk of prostate cancer. High Atlas Moroccans and Algerians show low frequency of UGT2B17del, a variant associated with high concentrations of testosterone and oestradiol.
... The lack of differentiation between Nabeul and these European populations may be attributed to their geographical proximity and historical past of the studied populations. Our results are in accordance with those of other studies based on uniparental inherited markers and autosomal biallelic markers [27][28][29][30]. A non-metric multidimensional scaling (NM-MDS) displaying the relationship between the Nabeul populations and other 16 populations is shown in Figure S2. ...
In the present study, the genetic variations of 17 X-STR markers (DXS8378, DXS9898, DXS7133, GATA31E08, GATA172D05, DXS6801, DXS7423, DXS6809, DXS6799, DXS7132, DXS9902, DXS6800, DXS6789, DXS10075, DXS10079, DXS6807, and DXS6803) were analyzed in 139 unrelated individuals in Nabeul, aiming to perform an X-STR database for anthropological and forensic purposes. Our results indicate that DXS6809 was the most polymorphic locus, whereas DXS6807 was the least informative marker. In addition, the obtained values for the statistical parameters of forensic interest, i.e., the power of discrimination in males (PDM) and females (PDF), as well as the mean exclusion chance in duos (MECD) and trios (MECT) have demonstrated that this panel of 17 X-STRs is highly informative and useful for forensic application and anthropological research. Additionally, pairwise genetic distances based on FST were calculated between Nabeul population and other populations extracted from the literature. Genetic distances were represented in a non-metric MDS plot and clustering of populations according to their geographic locations and their historical relationship was detected.
... However, this lack of association can be explained by the genetic characteristics of our population. Indeed, the Tunisian population, including Sousse, where most of our patients were recruited, shows a high heterogeneity (31). This might be due to the large influence of successive migration waves in this region. ...
Background
Pain and its opioid treatments are complex measurable traits. Responses to morphine in terms of pain control is likely to be determined by many factors, including the underlying pain sensitivity of the patient, along with nature and extent of the painful process, concomitant medications, genetic and other clinical and environmental factors. This study investigated genetic polymorphisms implicated in the inter-individual pain response variability to opioid treatment in the Tunisian population.
Methods
This prospective association study investigated seven variations in the OPRM1, OPRK1 and COMT gene, which encode Mu and KAPPA opioid receptors, and Catechol-O-methyltransferase enzyme respectively, in a cohort of 129 Tunisian cancer pain patients under oral morphine treatment. Genotyping was performed by simple probe probes on Light Cyler for rs17174629, rs1799972, rs1799971, rs1051659, rs1051660 and rs4680 and by PCR assay for the indel in the promoter region of OPRK1 (rs35566036). A statistical associations study between dose (continuous), dose escalation (yes/no) and SNP or haplotypes were investigated using linear multiple regressions and logistic regressions respectively adjusted on metastases and pain covariates in the R software.
Results
We detected significant association of the rs1051660 adjusted on metastasis and pain (P=0.02), no other association has been detected between the 7 polymorphisms screened and the dose of morphine needed for pain relief.
Conclusion
This can be explained by the strong genetic heterogeneity in the cosmopolitan areas where our patients were recruited for this study, compared to more homegenous population recruited in other studies.
