Background: Candidate gene and genome-wide association studies have both reproducibly identified several common Single Nucleotide Polymorphisms (SNPs) that confer type 2 diabetes (T2D) risk in European populations. Our aim was to evaluate the contribution to T2D of five of these established T2D-associated loci in the Arabic population from Tunisia. Methods: A case-control design comprising 884 type 2 diabetic patients and 513 control subjects living in the East-Center of Tunisia was used to analyze the contribution to T2D of the following SNPs: E23K in KCNJ11/Kir6.2, K121Q in ENPP1, the -30G/A variant in the pancreatic β-cell specific promoter of Glucokinase, rs7903146 in TCF7L2 encoding transcription factor 7-like2, and rs7923837 in HHEX encoding the homeobox, hematopoietically expressed transcription factor. Results: TCF7L2-rs7903146 T allele increased susceptibility to T2D (OR = 1.25 [1.06–1.47], P = 0.006) in our study population. This risk was 56% higher among subjects carrying the TT genotype in comparison to those carrying the CC genotype (OR = 1.56 [1.13–2.16], P = 0.002). No allelic or genotypic association with T2D was detected for the other studied polymorphisms. Conclusion: In the Tunisian population, TCF7L2-rs7903146 T allele confers an increased risk of developing T2D as previously reported in the European population and many other ethnic groups. In contrast, none of the other tested SNPs that influence T2D risk in the European population was associated with T2D in the Tunisian Arabic population. An insufficient power to detect minor allelic contributions or genetic heterogeneity of T2D between different ethnic groups can explain these findings.

Heightened expression of tumor necrosis factor (TNF)-α and lymphotoxin-α (LT-α) was associated with pregnancy complications, including idiopathic recurrent miscarriage (RM). Whereas TNF-α and LT-α gene polymorphisms affect serum cytokine concentrations, their contribution to RM is controversial. The single nucleotide polymorphisms (SNPs) TNF-α (−238G/A, −308G/A) and LT-α (+252A/G) were investigated in 350 RM women and 200 control women. Higher frequency of the TNF-α −238A, but not the TNF-α −308A or the LT-α+252G, allele was seen in patients, with comparable frequencies of TNF-α −238G/A, TNF-α −308G/A, and LT-α+252A/G genotypes seen between both groups, except for TNF-α −238G/G, which was lower in patients. Regression analysis confirmed the association of the TNF-α −238G/A SNP with idiopathic RM, and both TNF-α −308A/TNF −238G/LT-α+252G and TNF-α −308G/TNF-α −238A/LT-α+252G haplotypes played a susceptible role in idiopathic RM. TNF-α −238G/A and −238A/A, and LT-α+252G/G genotypes were positively associated only with exclusively early RM. This supports the concept of the association of TNF-α (−238G/A) and LT-α (+252A/G) polymorphic variants in idiopathic RM.

Background: Genetic variations in the calpain-10 gene (CAPN10), in particular the at-risk diplotype (112/121), were previously implicated with increased risk of type 2 diabetes (T2D). Methods: We examined the association of CAPN10 UCSNP-43 (rs3792267), UCSNP-19 (rs3842570), and UCSNP-63 (rs5030952) SNPs with T2D in 917 Tunisian T2D patients and 748 non-diabetic controls. CAPN10 genotyping was done by PCR-RFLP. Results: Enrichment of UCSNP-19 2R (minor) allele and 2R/2R genotype was found in T2D patients; the allele and genotype distribution of UCSNP-43 and UCSNP-63 alleles and genotypes were not significantly different between patient groups and non-diabetic control subjects. Regression analysis demonstrated progressive increases in T2D risk in 3R/2R [OR (95% CI) = 1.35 (1.08 - 1.68)] and 2R/2R [OR (95% CI) = 1.61 (1.20 - 2.18)] genotypes. Of the six haplotypes detected, enrichment of haplotype 111 (UCSNP-43/UCSNP-19/UCSNP-63) was seen in patients (Pc = 0.034); the distribution of the other haplotypes was comparable between patients and control subjects; neither haplotype 211 nor haplotype 212 was observed. Furthermore, the frequency of all CAPN10 diplotypes identified, including the "high-risk diplotype (112/121) reported for Mexican-Americans and Northern Europeans, were comparable between patients and controls. Conclusions: CAPN10 UCSNP-19 variant, and the 111 haplotype contribute to the risk of T2D in Tunisian subjects; no significant associations between CAPN10 diplotypes and T2D were demonstrated for Tunisians.

Factor V G1691A (FV-Leiden) and prothrombin (PRT) G20210A single nucleotide polymorphisms (SNPs) were associated with venous thrombosis among Caucasians. We assessed the contribution of both SNPs to the genetic susceptibility of deep venous thrombosis (DVT) among Lebanese and Tunisian patients. Subjects comprised 198 DVT patients and 540 healthy controls from Lebanon and 126 Tunisian DVT patients and 197 control subjects; FV-Leiden (MnlI) and PRT G20210A (HindIII) genotyping was done by PCR-RFLP. While the prevalence of FV-Leiden mutant A allele and the G/A and A/A genotypes were significantly higher among DVT patients from Lebanon and Tunisia, the association of PRT G20210A with DVT was pronounced among Lebanese but not Tunisian patients. The prevalence of PRT G20210A mutant A allele (P < 0.001 vs. P = 181) and G/A genotype (P < 0.001 vs. P = 0.994) was significantly higher among Lebanese but not Tunisians, respectively. While FV-Leiden was a common genetic risk factor for DVT in both communities, the contribution of PRT G20210A to the genetic susceptibility of DVT differed among Lebanese and Tunisians, which underscores the need to determine prothrombotic gene polymorphisms associated with DVT among Arab and Mediterranean basin communities. Am. J. Hematol. 81:641–643, 2006.

The aim of this study is to assess the association of nine SNPs on ADIPOQ on the PCOS risk among Saudi Arabian Women. A case–control study, including 162 cases and 162 controls in Saudi Arabia, was enrolled. Genotyping was carried out by the allelic discrimination method. Estimated haplotype frequencies were assessed using the maximum likelihood method. Results showed that ADIPOQ SNPs were not associated with PCOS for allelic and genotypic frequencies (p > .05). In haplotype estimation analysis, a significant positive association was detected between 21211 haplotype (rs2241766/rs1501299/rs2241767/rs3774261/rs17366743) in additive model with increased risk of PCOS (p = .009, OR = 2.16 [1.22–3.82] CI 95%). None of the nine SNPs illustrated significant association with the quantitative traits after multiple test corrections. These results support a significant association of 21211 haplotype (rs2241766/rs1501299/rs2241767/rs3774261/rs17366743) of ADIPOQ gene in Saudi women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is regarded as one of the most frequently encountered endocrine disorders and affects millions of young women worldwide, resulting in an array of complex metabolic alterations and reproductive failure. PCOS is a risk factor for diabetes mellitus, obstructive sleep apnea, obesity and depression in patients. Estrogen receptors (ESRs) are significant candidates in endocrine function and ovarian response in women. Moreover, microRNAs and long non-coding RNAs are emerging as principal mediators of gene expression and epigenetic pathways in various disease states. This study has characterized the clinical parameters in PCOS patients with comprehensive biochemical profiling compared to healthy controls and further examined the influence of allelic variations for estrogen receptor-α (ESR1 PvuII-rs2234693 T>C) and miRNA-146a (rs2910164 C>G) gene polymorphism on the risk of and susceptibility to PCOS. In this case-control study, we have used amplification refractory mutation specific (ARMS)-PCR to detect and determine the presence of these polymorphic variants in the study subjects. Our results demonstrated that most of the biochemical markers, which were analyzed in the study, show statistically significant alterations in PCOS patients, including fasting glucose, free insulin, HOMA-IR, LDL, HDL, cholesterol and hormones such as FSH, LH, testosterone and progesterone, which correlate with the established biochemical alterations in the disorder. Further, it is reported that for estrogen receptor-α (ESR1 PvuII-rs2234693 T>C), the frequency of the T allele (fT) was significantly higher among patients (0.64 vs. 0.44) compared to controls, while the frequency of the C allele (fC) was lower in patients (0.36 vs. 0.56) compared to controls. However, it was found that there was no association of an increased risk of PCOS with the ESR1 PvuII-rs2234693 C>T gene polymorphism. On the contrary, the study found strong association of miRNA-146a (rs2910164 C>G) gene polymorphism with an enhanced risk of PCOS. The frequency of the C allele (fC) was significantly higher among patients (0.52 vs. 0.36) compared to controls. The frequency of the G allele (fG) was found to be lower in patients (0.48 vs. 0.64) compared to controls. The codominant, dominant and recessive models display a statistically significant association of polymorphic variations with PCOS. Moreover, the G allele was associated strongly with PCOS susceptibility with an OR = 1.92 (95%) CI = (1.300–2.859), RR = 1.38 (1.130–1.691) p-value < 0.001.