Genome-wide association studies (GWAS) have identified the potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene, as a potential contributor to the pathogenesis of type 2 diabetes (T2D). Given the known genetic overlap between T2D and polycystic ovary syndrome (PCOS), the present study aimed to investigate the potential association between KCNQ1 gene variants and PCOS susceptibility in a population of Tunisian women. A total of 230 patients and 230 healthy controls were recruited for this case control study. The Rotterdam consensus criteria were used to diagnose patients with PCOS. Genotyping of three KCNQ1 variants (rs231361, rs151290 and rs2237895), was performed using allelic discrimination (real-time PCR). After excluding false positive associations using the false discovery rate adjustment and ensuring statistical power >80%, the present results suggested that the KCNQ1 gene may play a role in PCOS susceptibility. Specifically, the rs231361 variant showed a significant association with an increased risk of PCOS through multiple genetic inheritance models. Additionally, the A/A genotype of the rs231361 variant displayed a correlation with increased levels of triglycerides compared with those with the G/G wild-type and the G/A heterozygous genotypes. To the best of our knowledge, this is the first study to identify the KCNQ1 rs231361 variant as a potential genetic risk factor for PCOS. These findings have important implications for risk assessment and the development of personalized treatment approaches for affected women.

Background: Hypoadiponectinemia, a metabolic hallmark of obesity, is common in polycystic ovary syndrome (PCOS) yet the association of variants in the ADIPOQ gene with obesity in PCOS remains uncertain. To investigate whether ADIPOQ variants are associated with obesity in PCOS in relation to circulating adiponectin levels, and whether integrating genotypes, adiponectin, and a polygenic risk score (PRS) improves risk stratification. Methodology: In 324 Tunisian women with PCOS, classified as obese or non-obese by WHO criteria, serum adiponectin was measured, and nine ADIPOQ variants were genotyped using TaqMan assays. Associations with obesity were assessed using logistic regression, gene phenotype interaction analysis, and models incorporating a PRS; epistasis, QTL, and diplotypes were also evaluated. Results: Adiponectin levels were significantly lower in obese women and modestly predicted obesity (AUC = 0.605). Variants rs1501299 and rs3774261 were significantly associated with obesity under recessive models (OR up to 5.18, 95% CI [2.32–11.56], p = 7.14 × 10−5). Risk genotypes and haplotypes correlated with reduced adiponectin and increased obesity risk, with adiponectin levels significantly associated with the genotype–obesity relationships. A combined model including adiponectin, the two variants, and PRS outperformed single predictors. Conclusions:ADIPOQ rs1501299 and rs3774261 are associated with obesity in women with PCOS, with this association demonstrating a specific relationship with reduced adiponectin. Integrating genetic and biochemical markers improves metabolic risk profiling and supports personalized management.

BACKGROUND:Variants in the genes encoding anti-mullerian hormone (AMH) and its receptor 2 (AMHR2) have been identified as potential contributors to the development of polycystic ovary syndrome (PCOS). However, results from association studies examining their role in PCOS have been inconsistent. This study aims to investigate the potential association between AMH and AMHR2 gene variants and the risk of PCOS as well as their influence on serum AMH levels in a Tunisian cohort. METHODS:The case-control study recruited 327 PCOS women and 396 healthy controls. DNA was extracted and genotyped for three variants in the AMH gene namely, rs4807216, rs10407022 and rs8112524 as well as three variants in the AMHR2 gene, including rs2002555, rs11170553 and rs2272002, using the TaqMan SNP genotyping assay. Fasting serum AMH levels were quantified using ELISA. RESULTS:Significant metabolic differences were observed in the PCOS cohort, including higher BMI, and elevated levels of AMH, glucose, triglycerides, and cholesterol, along with lower FSH levels. The investigation of genetic associations between AMH and AMHR2 gene variants and PCOS susceptibility revealed notable genotype-specific correlations with lipid profiles. Specifically, the AMH rs8112524 A/A and G/A genotypes were correlated to increased triglyceride levels, while the AMHR2 rs2002555 G/G genotype, as well as the rs11170553 T/T and C/T genotypes, were correlated with decreased HDL levels. However, no significant allelic, genotypic or haplotypic associations were identified, nor was any substantial impact on serum AMH levels observed. Additionally, interaction and epistasis analyses indicated that the AMH and AMHR2 variants had no significant predictive capabilities regarding PCOS susceptibility. CONCLUSION:Although AMH and AMHR2 variants may not directly influence PCOS susceptibility, they could play a role in modulating lipid metabolism associated with the syndrome.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Although prior studies have shown that adiponectin synthesis is genetically determined and that its levels influence susceptibility to T2D, the results in this regard have been inconsistent. This study aims, to investigate the relationship between adiponectin gene variants with the risk of developing T2D among Tunisian women and in relation to their BMI status. A cohort of 491 Tunisian T2D women and 373 non-diabetic subjects participated in the study. Nine ADIPOQ variants namely rs16861194, rs17300539, rs266729, rs822395, rs822396, rs2241766, rs1501299, rs2241767 and rs3774261 were selected and genotyped using the TaqMan® SNP genotyping assay. Fasting serum adiponectin levels were quantified using ELISA. The results showed that only the rs17300539 variant exhibited a significant association with the risk of T2D. However, upon considering T2D group stratification based on BMI (normal weight [18-24.99 Kg/m2], overweight [25-29.99 Kg/m2] and obese [30-34.99 Kg/m2]), the ADIPOQ rs2241766 variant emerged as a contributing risk factor for increased BMI in obese women with T2D. Linear regression analysis revealed that the minor allele (A), (GA) and (AA) genotypes of rs17300539 as well as the (G) allele and (GG) genotype of rs2241766 were significantly associated with hypoadiponectinemia in T2D subjects. Two haplotypes namely GGCAATGAA and AGCCGTGGA, were identified as conferring a higher risk of T2D with the GGCAATGAA haplotype also correlating with hypoadiponectinemia. Our study underscores the importance of the rs17300539 variant and the GGCAATGAA haplotype in the risk of T2D and hypoadiponectinemia. Additionally, the presence of the rs2241766 variant highlights its association with 'diabesity' and hypoadiponectinemia among Tunisian T2D women.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder that affects women in their child-bearing age, and is associated with insulin resistance and type 2 diabetes. The etiology of PCOS involves multiple factors including genetic, metabolic and immunological factors. Interleukin − 10 (IL-10), as an anti-inflammatory cytokine, plays a critical role in this regard. We investigated the potential role of IL-10 gene variants in the development of PCOS in Tunisian population. 115 cases and 120 controls were recruited in the current case control study. Rotterdam consensus criteria were used to diagnose PCOS patients. Genotyping for IL-10, rs1800896, rs1800871 and rs1800872 variants, was performed by real time PCR. The results obtained showed that the minor allele frequency of rs1800896, rs1800871and rs1800872 were comparable between PCOS cases and control subjects (P = 0.30, P = 0.71, and P = 0.57 respectively). The distribution analysis revealed an unsignificant association of the three tested variants, in all genetic models. Haplotype analysis identified one haplotype CCA with a protective role in PCOS development (P = 0.05; OR (95

We explored the relation between FTO single gene variants (rs1861868, rs9939973, rs1421085, rs1121980, rs17817449, rs8050136, rs9939609, rs9930506, and rs8044769) and polycystic ovary syndrome (PCOS), in particular, according to the obesity status. This retrospective population-based case–control study involved women with PCOS (583) and 713 eumenorrheic control women; genotyping was done by real-time PCR. Significantly higher minor allele frequency (MAF) of rs9939973, rs17817449, rs9939609, and rs9930506 and lower MAF of rs1121980 were seen in PCOS cases. Lower risk of PCOS was associated with rs1121980 and rs8050136 heterozygous and minor allele-homozygous genotypes, while an elevated risk of PCOS was seen with minor allele-homozygous rs9939973, rs17817449, and r9939609 heterozygous and genotypes and minor allele-homozygous rs9930506 and rs8044769 genotype. While none of the tested FTO SNPs variants was associated with PCOS in normal body weight/lean subjects, rs9939973, rs9939609, and rs9930506 were negatively associated with PCOS in overweight subjects. In comparison, rs1861868 was negatively, while rs8044769 was positively associated with PCOS in obese subjects. Haplotype analysis identified haplotypes GACCTCTAT, AACCTCTAT, AACCTATAT and AGTTGCAGC, and GACCTCTAC to be positively associated with PCOS, while haplotypes GGTTGAAGC, GACCTATAT, GGTTGCAGC, and GATCTATAT were negatively associated with PCOS. Apart from GGTTGAAGC, these haplotypes remained associated with altered risk of PCOS after adjusting for covariates. In addition to rs17817449, rs9939609, rs9930506, and rs1121980, this study is the first to demonstrate association of rs9939973 and rs8044769 with altered risk of PCOS and the first to confirm the BMI dependency on the association of FTO variants with PCOS. This underscores the role of FTO gene variants as predisposing factors of PCOS.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

BackgroundDiabetic nephropathy is a highly destructive microvascular complication of diabetes. Genetic predisposition is involved in the pathogenesis of diabetic nephropathy, with multiple allelic polymorphisms associated with the development and progression of the disease, thereby increasing the overall risk. To date, no study is available that shows the association of matrix metalloproteinase-2 (MMP-2) gene polymorphisms with diabetic nephropathy risk. Thus, we investigated the potential genetic influence of MMP-2 promoter variants in the development of diabetic nephropathy in type 2 diabetic patients. MethodsIn total, 726 type 2 diabetic patients and 310 healthy controls were included in the study and genotyped for MMP-2, -1306C/T, -790T/G, -1575G/T and -735C/T by real-time PCR. The analysis of the outcomes was performed assuming three genetic models. The threshold for statistical significance was set at 0.05. ResultsThe results showed that the minor allele frequency of the -790T/G variant was significantly higher in patients with and without nephropathy compared to controls. Furthermore, the distribution analysis revealed a significant association of the -790T/G variant, in all genetic models, with increased risk of diabetic nephropathy that persisted after adjusting for key covariates. No significant associations between MMP-2, -1306C/T, -1575G/T, -735C/T and the risk of diabetic nephropathy were detected. Haplotype analysis identified two risk haplotypes GCGC and GTAC associated with diabetic nephropathy. ConclusionsThe present study is the first to demonstrate the allelic and genotypic association of the MMP-2-790T/G variant and two haplotypes with an increased risk of diabetic nephropathy in a Tunisian population with type 2 diabetes.

•Matrix metalloproteinases (MMPs) are involved in the development of multiples diseases•Several MMP-2 gene variants have been linked to the risk of development of DR but with mixed consequences.•MMP-2 variants rs243864 and 243866 are related to the susceptibility to DR and the progression of the disease.•GCTC, TTTC, and GCTT haplotypes were associated with the risk of DR.

BACKGROUND:Previous studies examined the association of genetic variation in progesterone receptor (PR) gene (PGR) with ovarian cancer, possibly by altering the expression of PR-B isoform, but with mixed outcome. OBJECTIVE:This study evaluated the association of PGR variants with ovarian cancer and associated features. METHODS:This was a retrospective case-control study, which involved 82 women with ovarian cancer and 95 cancer-free women who served as controls. Genotyping was done by Taqman® SNP genotyping by qRT-PCR. The PGR variants tested were rs471767 (A > G), rs590688 (G > C), and rs10895068 (G > A). Stratification analyses were used for testing the correlation between the PGR variants with ovarian cancer susceptibility according to menstruation status, FIGO classification, pathological grade, and chemotherapy. RESULTS:Significantly lower minor allele frequency (MAF) of rs10895068 was seen among ovarian cancer patients, thereby imparting disease protective nature to this variant. Significant association of rs10895068 genotypes with ovarian cancer was seen under the dominant model, but not other genetic models. FIGO classification correlated positively with rs471767 and rs10895068, while rs10895068 correlated positively with lymph node positivity. Three-locus haplotype analysis identified ACA and HCG haplotypes to be negatively associated with the risk of ovarian cancer. CONCLUSIONS:This report confirms the contribution of PGR variants, specifically the rs10895068 (+331G/A) the etiology of ovarian cancer.

Aims: Genetic variations mediating MMP-2 expression may result in individual differences in susceptibility to particular diseases. Our aim was to investigate the possible association of certain MMP-2 gene variants with the susceptibility of type 2 diabetes (T2D) in a Tunisian population. Subjects and methods: A retrospective case-control study involving 310 normoglycemic control subjects and 791 T2D patients was conducted. Genotyping of MMP-2 variants was performed by real time PCR. Results: Minor allele frequencies (MAF) of the rs243865 and the rs243866 MMP-2, were significantly different between T2D cases and controls. Setting homozygous wild-type genotype carrier as reference, a reduced risk of T2D was seen with the rs243865 and the rs243866 genotypes. Haploview analysis revealed limited linkage disequilibrium between the tested MMP-2 and variants, with most haplotypes (99.5%) captured by 7 MMP-2 haplotypes. Taking the GCCC haplotype as reference for MMP-2 (OR = 1.00), a reduced frequency of TTCC haplotypes (P = 0.04) and the GTCC haplotype (P = 3.5 . 10(-5)) was noted in T2D which indicates a protective nature of these two haplotypes for T2D development. Conclusion: To the best of our knowledge, the present study is the first to demonstrate a consistent association of the rs243865 and rs243866 genotype with a protection for T2D. (C) 2021 Elsevier Inc. All rights reserved.

Preeclampsia (PE) is a multi-system disorder that is specific to human pregnancy. Inadequate oxygenation of uterus and placenta is considered as one of the leading causes for the disease. MicroRNA-210(miR-210) is one of the prime molecules that has emerged in response to hypoxia. The objective of this study was to determine miR-210 expression patterns in plasma from severe PE and mild PE patients, and how that affects the expression of miR-210 target genes. The expression levels of miR-210 were validated using reverse transcription-quantitative PCR in plasma of severe PE (15) and mild PE (15) patients in comparison to controls subjects (15) with normal pregnancy. Then, the association between miR-210 and its downstream genes was validated by using human miR-210 targets RT2 profiler PCR Array. Both the categories (mild and severe) showed significantly high miR-210 expression levels. Also out of the 84 hypoxia miR-210 associated genes screened using mRNA, 18 genes were found to be differentially expressed in severe PE whereas 16 genes in mild PE cases with varying magnitude. All the genes in both the PE groups were found downregulated in comparison to controls. These downregulated genes expressed in both the cases were shown to be participating in immunosuppression, apoptosis, cell growth, signaling, angiogenesis, DNA repair. This study provides novel data on the genes that work downstream of miR-210 and how dysregulated expression of miR-210 can affect their expression and in turn functioning which can be associated with PE risk and severity. This study is the very first to determine the effect of miR-210 expression levels on associated genes in plasma samples.

PROBLEM:We investigated the association between idiopathic recurrent pregnancy loss (RPL) and HLA-DPB1, HLA-DQB1, and HLA-DRB1 alleles and DPB1-DQB1-DRB1 haplotypes.METHOD OF STUDY:Case-control retrospective study involved 93 Lebanese women with unexplained RPL, and 113 multiparous Lebanese women with two or more successful pregnancies, and no miscarriages who served as controls. DPB1, DQB1, and DRB1 genotyping was performed by PCR-SSP.RESULTS:Expected and observed DRB1, DQB1, and DPB1 frequencies were comparable, and HLA genotype frequencies were in Hardy-Weinberg equilibrium. Significantly higher frequencies of DRB1*04:01:01 and DRB1*08:01:01, and decreased DRB1*07:01:01 frequency were seen in RPL cases than in controls. On the other hand, the distribution of DQB1 alleles was comparable between cases and control groups. Significantly lower frequencies of DPB1*04:01:01 and DPB1*14:01:01 were seen in women with RPL than control subjects. While the frequency DPB1*02:01:01 was markedly higher in RPL cases than in controls, the difference was not significant. DPB1-DQB1-DRB1 haplotype analysis identified haplotype DPB1*04:01:01-DQB1*03:02:01-DRB1*04:01:01 to be positively associated, while haplotype DPB1*04:01:01-DQB1*02:01:01-DRB1*07:01:01 to be negatively associated with RPL. Of these two haplotypes, only DPB1*04:01:01-DQB1*02:01:01-DRB1*07:01:01 remained significant after correction for multiple tests (Pc  = .0008).CONCLUSION:Our results confirm an association of select DRB1 and DPB1 alleles with RPL in Lebanese women, and the first to identify DPB1-DQB1-DRB1 linked with altered RPL susceptibility, further highlighting the immunological/inflammatory nature of RPL.

Abstract BACKGROUND. The ATP-sensitive K (KATP) channel regulates insulin sensitivity, by linking insulin secretion to changes in blood glucose levels. HYPOTHESIS. Kir6.2 is a specific point mutation in KCNJ11 gene, which encodes the pore-forming subunit of the pancreatic KATP channel, and was reportedly linked with impaired insulin secretion and diabetes development. METHODOLOGY. We investigated whether the E23K Kir6.2 polymorphism is associated with the presence of diabetic retinopathy (DR) in 804 Tunisian type 2 diabetes (T2DM) patients. Genotype analysis was performed by real-time PCR. MAJOR RESULTS. While the E23K minor allele frequency was comparable between T2DM patients with (DR) and without (DWR) retinopathy (32.3% vs. 31.9%; P = 0.919), the distribution of E23K genotypes was significantly different between both T2DM patient groups (P = 0.024). In T2DM patients with HbA1c values < 7.0%, the T/T genotype was present at higher frequency in DR (14.9%) than in DWR (4.3%) patients (P = 0.007). Regression analysis confirmed the association of Kir6.2 K/K genotype with DR in patients with normal HbA1c (P = 0.022; OR = 12.70; 95% CI = 1.46-10.25). CONCLUSIONS. The E23K Kir6.2 polymorphism is associated with DR in T2DM in an HbA1c-dependent manner, thereby suggesting that Kir6.2 E23K homozygosity may predict the extent of hyperglycemic control in DR patients.

Background: An association between Apolipoprotein E (Apo E) alleles and genotypes and diabetic nephropathy (DN) was suggested, but with inconsistent results. We tested the relationship between serum lipids, Apo E alleles and genotypes with type 2 diabetes (T2DM), and DN pathogenesis. Methods: Study subjects comprised 1389 normoglycemic controls, and 1422 T2DM patients, of whom 825 were normoalbuminuric (DWN), and 597 presented with nephropathy (DN). Results: Significantly lower Apo epsilon 2, and higher Apo epsilon 4 allele frequencies was seen among T2DM patients than controls. Significantly higher frequency of epsilon 3/epsilon 4, and lower frequencies of epsilon 3/epsilon 3, epsilon 2/epsilon 3, and epsilon 4/epsilon 4 carriers was seen among T2DM cases. Apo epsilon 2-carrying individuals were more frequently found in controls than in patients, while significantly higher frequency of epsilon 4-carrying genotypes was seen in T2DM cases. Significantly higher epsilon 2, and lower epsilon 3 allele frequencies were noted for DN group compared to DWN group. Significantly higher frequency of epsilon 2-containing epsilon 2/epsilon 3 and epsilon 2/epsilon 4, and lower frequencies of epsilon 3/epsilon 3 carriers was seen among DN cases. Apo epsilon 3/epsilon 3 was associated with higher total cholesterol, LDL-cholesterol, and triglyceride levels in DN patients, and significantly higher triglyceride levels were seen in epsilon 2/epsilon 3-carrying DN patients. Logistic regression analysis confirmed the association of Apo epsilon 3-containing epsilon 3/epsilon 3, epsilon 2/epsilon 3, and epsilon 3/epsilon 4, and Apo epsilon 2-containing epsilon 2/epsilon 4 with DN, after controlling for key covariates. Conclusion: The results of this case-control study provide evidence that the epsilon 2 and epsilon 3 alleles of APOE modify lipid profile, and constitute independent risk factors of DN in type 2 diabetes. The molecular mechanisms underlying this risk is discussed.

Background: Vascular endothelial growth factor (VEGF) contributes to type 2 diabetes (T2DM) pathogenesis, and genetic variations in VEGFA gene were suggested to influence VEGF secretion and T2DM pathogenesis. Aim: To evaluate the association of specific VEGFA variants with altered VEGF levels, and with T2DM among Tunisians. Subjects and methods: A retrospective case-control study, performed on 815 T2DM patients, and 805 healthy controls. VEGF levels were measured by ELISA, genotyping of VEGFA variants was done by allelic exclusion method (real-time PCR). Results: MAF of rs1570360, rs2010963, rs25648, rs833068, rs3025036, and rs3025039 were significantly different between T2DM cases and controls. Increased T2DM risk was associated with rs699947, rs1570360, and rs3025020, while reduced T2DM risk was seen with rs1547651, rs2010963, rs25648, rs3025036, and rs3025039 genotypes, thus assigning T2DM susceptibility and protection, respectively. Reduced VEGF levels were associated with rs833061, rs2010963, and rs3025039 heterozygosity and rs3025036 major allele homozygosity in T2DM cases, while increased VEGF levels were seen in rs833070 homozygous major allele genotype. Both rs699947 and rs1570360 positively, while rs2010963 and rs3025036 negatively correlated with fasting glucose. In addition, rs699947 positively correlated with LDL-cholesterol, and rs3025039 positively correlated with diabetes duration, but negatively with HbAl c and serum triglycerides. Haploview analysis identified Block 1 containing 8 loci, and Block 2 with the remaining 3 loci. Haplotypes ACTGCCGG and AACGGCGA (Block 1) were negatively associated with T2DM, while haplotype CCC was positively and haplotype CGC (Block 2) were negatively associated with T2DM. Conclusion: This study confirms the contribution of altered VEGF secretion, resulting from genetic variation in VEGFA gene into T2DM pathogenesis, hence supporting role for VEGFA as T2DM candidate locus.

OBJECTIVE:Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting approximately one in seven women who experience androgen excess, menstrual cycle irregularities, frequent anovulation and a tendency for central obesity and insulin resistance. Chronic subclinical inflammation is now recognised as being common in the context of PCOS, which led to the postulation that PCOS may fundamentally be an inflammatory process. This study aimed to: (1) evaluate serum C reactive protein (CRP)/albumin ratio as a potential predictive biomarker for PCOS; (2) compare the relationship between CRP/albumin and PCOS to variables classically associated with the syndrome. DESIGN:Case-control study. SETTING:Adult obstetrics/gynaecology, endocrinology and outpatient clinics; university hospital in Bahrain. PARTICIPANTS:200 premenopausal women with a diagnosis of PCOS, and 119 ethnically matched eumenorrheic premenopausal women. MAIN OUTCOME MEASURES:CRP/albumin ratio, anthropometric measures, insulin resistance, androgen excess. RESULTS:Independent of body mass index (BMI), receiver operating characteristic curve for CRP/albumin ratio as a selective biomarker for PCOS was 0.865 (95% CI 0.824 to 0.905), which was more sensitive than CRP alone. Binary regression analysis showed that CRP/albumin ratio outperformed classical correlates, Free Androgen Index and insulin resistance, in predicting PCOS for every BMI category. CONCLUSION:CRP/albumin ratio, a marker for inflammation related to metabolic dysfunction, was found to have a stronger association with PCOS than either androgen excess or insulin resistance. Inflammation is known to be influenced by adiposity, but relative to controls, women with PCOS have higher levels of CRP/albumin irrespective of BMI. These findings support the view that inflammation plays a central role in the pathophysiology of PCOS.

Background To investigate the relationship between changes in circulating soluble CD40 ligand (sCD40L) levels and the presence and severity of type 2 diabetic retinopathy (DR). Subjects and methods sCD40L plasma concentrations were measured in 205 type 2 diabetes (T2DM) patients without DR (DWR; n =50) and with DR (n =155), the latter subdivided into non-proliferative diabetic retinopathy [NPDR; n =98 (63.2 %)], or proliferative retinopathy [PDR; n = 57 (36.8 %)] patients. Results Receiver operating characteristic analysis provided good discriminatory power for sCD40L as predictor of DR presence, with high sensitivity and specificity. Categorizing DWR and DR patients into sCD40L quartiles, based on sCD40L concentrations in T2DM without DR, demonstrated statistically significant gradual increase in DR risk with increasing sCD40L levels. sCD40L levels were significantly higher in DR compared to DWR patients. Plasma sCD40L levels differed significantly according to DR severity, and correlated with diabetes duration, dyslipedimea, nephropathy, and presence of DR, but not with gender, age, SBP, DBP, FPG, HbA1c, T2DM medications. Linear regression analysis confirmed the association of increased sCD40L levels with DR, independent of others parameters; mean plasma sCD40L levels differing significantly according to DR severity. Conclusion Plasma sCD40L levels were positively associated with DR. The significant finding here is that sCD40L levels can be predictors of DR severity.

Background and aim: Polycystic ovary syndrome (PCOS) is a common endocrine disorder, and results from interaction between modifiable and non-modifiable factors, including genetic predisposition. Previous genomewide association studies and meta-analysis identified DENND1A as PCOS susceptibility locus in some, but not all populations. We investigated whether the association of DENNDIA gene variants with PCOS was similar between Tunisian and Bahraini Arab women. Subjects and methods: This was retrospective case-control study. Study subjects comprised 320 women with PCOS, and 446 age-and ethnically-matched control women. Genotyping of DENNDIA rs10818854, rs2479106, and rs10986105 variants was done by real-time PCR. Results: Minor allele frequency of rs10818854 and rs10986105 DENND1A variants were significantly higher among women with PCOS. Setting homozygous wild-type genotype carrier as reference, rs10818854 and rs10986105 were associated with increased risk of PCOS, which persisted after controlling for key covariates, while reduced PCOS risk was seen with only rs2479106 under the additive model. This assigned PCOS susceptibility and protective nature to these genotypes, respectively. Both rs10818854 and rs10986105 were positively associated with HOMA-IR and AMH in women with PCOS. Haploview analysis revealed limited linkage disequilibrium between the tested DENNDIA variants. Extensive diversity in haplotypes assignment was seen, with most haplotypes (99.5%) captured by 5 haplotypes. Taking GAT haplotype as reference, AAG, and GAG haplotypes were positively, while GAT haplotype was negatively associated with PCOS. Conclusion: The association of DENNDIA rs10818854 and rs10986105 variants with PCOS in Tunisian but not Bahraini women confirms the dependence of this association on the ethnic/racial origin of study subjects.