Rs9939609 Variant Research Articles

The association between the melatonin receptor 1B gene polymorphism rs10830963 and glucose levels in type 2 diabetes

IntroductionMelatonin is a pineal hormone under the control of the biological clock, which is located in the hypothalamus and regulated by light exposure. Melatonin receptors have been found throughout the body in many tissues including pancreatic islet cells, reflecting the widespread effects of melatonin on physiological functions such as energy metabolism and the regulation of body weight. Several lines of evidence suggest that melatonin may play a role in glucose metabolism.Aim of the workTo investigate the association between diabetes mellitus (T2D) and the variants rs10830963 in the melatonin receptor 1B gene (MTNR1B) locus in a sample of the Egyptian population.Patients and methodThis was a case–control study conducted in the internal medicine department at El-Kasr El-Aini Hospital, Cairo University.It included 30 diabetic individuals (type 2) compared with 20 healthy individuals. All individuals included in the study were subjected to a detailed history taking, complete physical examination, body composition evaluation, and laboratory testing including blood picture, blood urea nitrogen, creatinine, lipid profile, and genotyping of melatonin receptor B1. Diabetic individuals were subtyped into three groups: (a) Diabetic patients without complications. (b) Diabetic patients with microvascular complications. (c) Diabetic patients with macrovascular complications.ResultsStatistical analysis revealed a significant positive correlation between the MTNR1B polymorphism rs10830963 and glucose levels in type 2 diabetes.ConclusionThe study confirmed that individuals having the MTNR1B gene polymorphism are at a greater risk of developing type 2 diabetes and having higher blood glucose levels and are more prone to be dyslipidemic than others who have no polymorphism.

Effect of six type 2 diabetes susceptibility loci and the FTO variant RS9939609 on obesity in Pakistani obese subjects

Objectives: We aimed to analyze effect of six type 2 diabetes susceptibility loci, rs3923113 (GRB14), rs18681329 (ST6GAL1), rs1802295 (VPS26A), rs7178572 (HMG20A), rs2028299 (AP3S2), and rs4812829 (HNF4A) and FTO polymorphism (rs9939609) reported to have contradictory results in Caucasians and Asians, on obesity. Association between the SNPs and biochemical and anthropometric parameters was analyzed to deduce mechanism of action.

Single nucleotide polymorphisms of the FTO gene and cancer risk: an overview.

The FTO (fat mass and obesity-associated) gene has a strong linkage disequilibrium block, within which SNPs have been identified that are involved in the development of obesity. Recently some of these variants have also been associated with cancer. However, identification of the possible mechanisms that could explain these associations has proven to be elusive. It has been found that FTO polymorphisms can regulate the expression of genes at large kilobases of distance as well as the expression of the FTO gene itself, and regions for transcription factor binding. To date it has been observed that variants rs9939609, rs17817449, rs8050136, rs1477196, rs6499640, rs16953002, rs11075995 and rs1121980 are associated with the risk of developing cancer. Some studies have produced negative results when comparing the same polymorphisms, but make a simple association between polymorphic variants and cancer, have proved difficult because this relation is by nature multifactorial. A certain degree of variation resulting from the improper design of studies or processing of data can lead to erroneous conclusions. However, it is now unquestionable that certain FTO polymorphisms regulate genetic expression related to cancer susceptibility, although this field is just beginning to be understood.

Investigation of polymorphisms rs7903146 and rs12255372 in the TCF7L2 gene in biochemical markers of severity of type 2 diabetes mellitus (T2DM) in a sample of adults with T2DM

Diabetes mellitus type 2 (DM2) is a metabolic disease that involves complex multifactorial genetic and environmental factors [1]. Studies on the molecular genetics has suggested that many genes may be important in susceptibility to DM26. Recently, large-scale studies such as genome-wide associations studies (GWAS) have shown several important genes associated with T2DM. Among these genes, one of the most strongly associated with the disease is TCF7L2. This gene has many polymorphisms described, however the majority of studies indicate variants rs7903146 and rs12255372 as the most important within this gene.

Association between Mediterranean and Nordic diet scores and changes in weight and waist circumference: influence of FTO and TCF7L2 loci

Several studies have shown that adherence to the Mediterranean Diet measured by using the Mediterranean diet score (MDS) is associated with lower obesity risk. The newly proposed Nordic Diet could hold similar beneficial effects. Because of the increasing focus on the interaction between diet and genetic predisposition to adiposity, studies should consider both diet and genetics. We investigated whether FTO rs9939609 and TCF7L2 rs7903146 modified the association between the MDS and Nordic diet score (NDS) and changes in weight (Δweight), waist circumference (ΔWC), and waist circumference adjusted for body mass index (BMI) (ΔWCBMI). We conducted a case-cohort study with a median follow-up of 6.8 y that included 11,048 participants from 5 European countries; 5552 of these subjects were cases defined as individuals with the greatest degree of unexplained weight gain during follow-up. A randomly selected subcohort included 6548 participants, including 5496 noncases. Cases and noncases were compared in analyses by using logistic regression. Continuous traits (ie, Δweight, ΔWC, and ΔWCBMI) were analyzed by using linear regression models in the random subcohort. Interactions were tested by including interaction terms in models. A higher MDS was significantly inversely associated with case status (OR: 0.98; 95% CI: 0.96, 1.00), ΔWC (β = -0.010 cm/y; 95% CI: -0.020, -0.001 cm/y), and ΔWCBMI (β = -0.008; 95% CI:-0.015, -0.001) per 1-point increment but not Δweight (P = 0.53). The NDS was not significantly associated with any outcome. There was a borderline significant interaction between the MDS and TCF7L2 rs7903146 on weight gain (P = 0.05), which suggested a beneficial effect of the MDS only in subjects who carried 1 or 2 risk alleles. FTO did not modify observed associations. A high MDS is associated with a lower ΔWC and ΔWCBMI, regardless of FTO and TCF7L2 risk alleles. For Δweight, findings were less clear, but the effect may depend on the TCF7L2 rs7903146 variant. The NDS was not associated with anthropometric changes during follow-up.

Obesity as a causal risk factor for deep venous thrombosis: a Mendelian randomization study.

To test the hypothesis that obesity is causally associated with deep venous thrombosis (DVT). A Mendelian randomization design. The Copenhagen General Population Study and the Copenhagen City Heart Study combined. Body mass index (BMI) measurements were available for 87, 574 individuals of Danish descent from the adult general population. All subjects completed questionnaires and were genotyped for the FTO rs9939609 variant. First events of DVT with or without pulmonary embolism (PE). The results were assessed using Cox regression, instrumental variable analysis and Poisson regression. Observationally, the risk of DVT increased with increasing BMI (P-trend < 0.0001). The multivariable-adjusted hazard ratio [95% confidence interval (CI)] for DVT was 1.3 (1.1-1.6) in overweight, 1.8 (1.4-2.2) in moderately obese and 3.4 (2.6-4.6) in severely obese compared with normal-weight individuals. For DVT complicated by PE, corresponding hazard ratios (95% CI) were 1.2 (0.8-1.8), 2.1 (1.3-3.5) and 5.1 (2.8-9.2). FTO AA versus TT genotype was associated with a 2.4% increase in BMI with hazard ratios (95% CI) of 1.09 (0.95-1.25) for DVT and 1.54 (1.12-2.10) for DVT complicated by PE. In instrumental variable analysis, the causal odds ratio (95% CI) for an increase in BMI of 1 kg m(-2) was 1.13 (0.92-1.39) for DVT alone and 1.86 (1.14-3.02) for DVT complicated by PE. The absolute 10-year risk of DVT in a high-risk group (i.e. those aged >60 years and homozygous for Factor V Leiden) was 35% in obese individuals and 18% in normal-weight individuals. A strong observational association between obesity and DVT with or without PE, supported by a direct genetic association between the obesity-specific locus FTO and DVT with PE, implies that obesity is likely to be causally associated with DVT.

Clinical and non-targeted metabolomic profiling of homozygous carriers of Transcription Factor 7-like 2 variant rs7903146.

An important role of the type 2 diabetes risk variant rs7903146 in TCF7L2 in metabolic actions of various tissues, in particular of the liver, has recently been demonstrated by functional animal studies. Accordingly, the TT diabetes risk allele may lead to currently unknown alterations in human. Our study revealed no differences in the kinetics of glucose, insulin, C-peptide and non-esterified fatty acids during an OGTT in homozygous participants from a German diabetes risk cohort (n = 1832) carrying either the rs7903146 CC (n = 15) or the TT (n = 15) genotype. However, beta-cell function was impaired for TT carriers. Covering more than 4000 metabolite ions the plasma metabolome did not reveal any differences between genotypes. Our study argues against a relevant impact of TCF7L2 rs7903146 on the systemic level in humans, but confirms the role in the pathogenesis of type 2 diabetes in humans as a mechanism impairing insulin secretion.

FTO genotype, dietary protein, and change in appetite: the Preventing Overweight Using Novel Dietary Strategies trial

A common obesity-risk variant rs9939609 in the fat mass- and obesity-associated (FTO) gene was recently shown to affect appetite, and the gene is sensitive to the regulation of amino acids. We examined the interaction between FTO genotype and protein intake on the long-term changes in appetite in a randomized controlled trial. We genotyped FTO rs9939609 in 737 overweight adults in the 2-y Preventing Overweight Using Novel Dietary Strategies trial and assessed 4 appetite-related traits including cravings, fullness, hunger, and prospective consumption. We showed that dietary protein significantly modified genetic effects on changes in food cravings and appetite scores at 6 mo after adjustment for age, sex, ethnicity, baseline body mass index, weight change, and baseline value for respective outcomes (P-interaction = 0.027 and 0.048, respectively). The A allele was associated with a greater decrease in food cravings and appetite scores in participants with high-protein-diet intake (P = 0.027 and 0.047, respectively) but not in subjects in the low-protein-diet group (P = 0.384 and 0.078, respectively). The weight regain from 6 to 24 mo attenuated gene-protein interactions. Protein intakes did not modify FTO genotype effects on other appetite measures. Our data suggest that individuals with the FTO rs9939609 A allele might obtain more benefits in a reduction of food cravings and appetite by choosing a hypocaloric and higher-protein weight-loss diet. This trial was registered at clinicaltrials.gov as NCT00072995.

Effects of Melatonin Receptor 1B Gene Variation on Glucose Control in Population from Bosnia and Herzegovina

Common variants in MTNR1B, encoding melatonin receptor 1B, have been recently associated with impaired glucose homeostasis and an increased risk for developing Type 2 diabetes (T2D). In this study we investigated the association of MTNR1B variant rs10830963 with T2D and related quantitative traits in a population from Bosnia and Herzegovina (BH). A total number of 268 subjects were recruited in the study (162 T2D patients and 106 nondiabetic controls). Subjects were genotyped for MTNR1B rs10830963 SNP by using hydrolysis probes. Our data showed that the prevalence of the MTNR1B rs10830963 risk G-allele in BH population was 26%. Furthermore, we demonstrated a significant association of MTNR1B rs10830963 variant with fasting plasma glucose (FPG) levels in nondiabetic subjects. Under the additive genetic model, each variant G-allele was associated with an increased FPG levels of 0.29 mmol/L (95% CI 0.12, 0.46, p = 0.001). Strikingly, our results also showed a significant association of this MTNR1B polymorphism with increased glycated hemoglobin (HbA1c) levels in nondiabetic subjects (p = 0.040, additive genetic model). An association of the MTNR1B variant rs10830963 with T2D risk was not detected in our cohort. In conclusion, here we have demonstrated the association between the common MTNR1B rs10830963 variation and fasting plasma glucose levels in BH population. Furthermore, the influence of this polymorphism on the HbA1c levels was also shown in this study, further strengthening its role in blood glucose control.

Abstract P183: FTO Genotype, Dietary Protein, and Change in Appetite: the Pounds Lost trial

Objective: A common "obesity-risk" variant rs9939609 in the FTO gene was recently found to affect appetite, and the gene is sensitive to regulation of amino acids. We examined the interaction between FTO genotype and protein intake on the long-term changes in appetite in a randomized controlled trial. Research Design and Methods: We genotyped FTO rs9939609 in 737 overweight adults in the 2-year Preventing Overweight Using Novel Dietary Strategies (Pounds Lost) trial and assessed four appetite related traits including cravings, fullness, hunger, and prospective consumption. Results: We found that dietary protein significantly modified genetic effects on changes in food cravings at 6 months, after adjustment for age, sex, ethnicity, baseline body mass index, weight change, baseline value for food cravings (P for interaction=0.027). The A allele was associated with a greater decrease in food cravings among the participants with high protein diet intake (P=0.027), but not in those low protein diet group (P= 0.384). Weight regain from 6 months to 24 months attenuated the gene-protein interactions. Protein intakes did not modify the FTO genotype effects on other appetite measures. Conclusions: Our data suggest that individuals with the FTO rs9939609 A allele might obtain more benefits in reduction of food cravings by choosing a hypocaloric and higher protein weight-loss diet. Keywords: diet, genetic variation, food cravings, gene-diet interaction, weight-loss trial

Transcription factor 7-like 2 (TCF7L2) gene polymorphism and clinical phenotype in end-stage renal disease patients

Variants of the transcription factor 7-like 2 gene (TCF7L2) have been associated with type 2 diabetes and cardiovascular disease in different populations. Here we investigated the potential association of the rs7903146 polymorphism in the TCF7L2 gene with clinical profile of end-stage renal disease (ESRD) patients. We examined a cohort of 1065 ESRD patients with diabetic and non-diabetic renal disease. The control group consisted of 924 healthy individuals. All subjects were genotyped for the rs7903146 single nucleotide polymorphism by polymerase chain reaction. The genotype distribution and allele frequencies were significantly different between ESRD patients and controls (p < 0.01). The OR for the TT genotype was 2.81 (95 % CI 2.08–3.79). Genotype and allele frequencies were compared between subgroups of patients with different clinical phenotypes. The frequency of the T allele was significantly higher in patients with diabetic nephropathy versus non-diabetic renal disease (p = 0.007, OR 1.70, 95 % CI 1.36–2.11). The statistically significant differences were demonstrated between patients with and without cardiovascular disease, with the OR for T allele 1.57 (95 % CI 1.31–1.90). The odds ratio for TT genotype was 2.38 (95 % CI 1.62–3.51). In our study the T allele of the rs7903146 SNP in the TCF7L2 gene confers the risk of developing diabetic nephropathy. We described for the first time a strong relationship between the TCF7L2 gene variant rs7903146 and cardiovascular disease in end-stage renal disease patients.

Transcription factor 7-like 2 (TCF7L2) gene polymorphism rs7903146 is associated with stroke in type 2 diabetes patients with long disease duration

Associations between TCF7L2 SNP and diabetic complications and diabetes-related factors were investigated. Subjects with rs7903146 variant had significantly higher prevalence of stroke (24.1% vs. 11.1%; P=0.039) among subjects exhibiting a long disease duration (≥10 years). In conclusion, the TCF7L2 SNP variant may confer a higher risk of stroke in diabetic patients.

Gene-Gene Interplay and Gene-Diet Interactions Involving the MTNR1B rs10830963 Variant with Body Weight Loss

Background/Aims: Investigation of the genetic makeup may facilitate the implementation of more personalized nutritional interventions. The aims were to examine whether the rs10830963 MTNR1B polymorphism affects weight loss in response to a hypocaloric diet and to find potential gene-gene interplays and gene-diet interactions. Methods: 167 subjects enrolled in a personalized nutritional intervention for weight loss (3-6 weeks) were examined for anthropometric measurements, dietary habits and physical activity at baseline and at the first follow-up visit. Three polymorphisms, which have previously been associated with body weight regulation, rs10830963 (MTNR1B), rs9939609 (FTO) and rs17782313 (MC4R), were analyzed using the Luminex® 100/200™ System. Results: After adjusting for covariates, females with the rs10830963 CG/GG genotype showed lower weight loss than those with the CC genotype. In the total population, carriers of variant alleles of both FTO and MC4R showed a significant association with MTNR1B and weight loss outcome. Moreover, among women, higher total protein and animal protein intakes were associated with a lower weight loss in G allele carriers of the MTNR1B variant. Conclusions: Our data evidenced that rs10830963 MTNR1B polymorphism could be associated with individual differences in weight loss induced by a hypocaloric diet. This association was influenced by FTO and MC4R loci and modified by baseline protein intake.

Rs7903146 variant of TCF7L2 gene and rs18012824 variant of PPARG2 gene (Pro12Ala) are associated with type 2 diabetes mellitus in Novosibirsk population

Aim. To investigate the association of polymorphisms in TCF7L2 and PPARG2 genes with type 2 diabetes mellitus (T2DM) in Novosibirsk population. Materials and Methods. We examined 391 patients with T2DM and 556 individuals with normal glucose metabolism. Allelic identification was performed with TaqMan technique, implementing allele-specific real-time PCR. Results. Analysis shows that allelic frequency distribution of rs1801282 variant of PPARG2 gene and rs7903146 variant of TCF7L2 differs significantly between the study and control groups (OR [CI 95%]=1.44 [1.12?1.85], p=0.005 and OR [CI 95%]=1.57 [1.17?2.10], p=0.003, respectively). T2DM patients with T/T genotype of rs7903146 variant of TCF7L2 gene had lower BMI (p=0.02). Observed combination of risk alleles reached 99%. Combined beta-cell dysfunction and insulin resistance genotypes were identified in 56% of tested subjects, isolated insulin resistance ? in 42.2% of subjects, and isolated beta-cell dysfunction ? in 0.8% of subjects. Conclusion. Our data shows that carrier state of 12Pro rs1801284 variant of PPARG2 gene and T-allele rs7903146 variant of TCF7L2 gene are associated with T2DM in Novosibirsk population, increasing its risk 1.44 and 1.57 times, respectively. Combination of these polymorphisms was observed in 99% of patients with T2DM.

SLC30A8 Nonsynonymous Variant Is Associated With Recovery Following Exercise and Skeletal Muscle Size and Strength

Genome-wide association studies have identified thousands of variants that are associated with numerous phenotypes. One such variant, rs13266634, a nonsynonymous single nucleotide polymorphism in the solute carrier family 30 (zinc transporter) member eight gene, is associated with a 53% increase in the risk of developing type 2 diabetes (T2D). We hypothesized that individuals with the protective allele against T2D would show a positive response to short-term and long-term resistance exercise. Two cohorts of young adults-the Eccentric Muscle Damage (EMD; n = 156) cohort and the Functional Single Nucleotide Polymorphisms Associated with Muscle Size and Strength Study (FAMuSS; n = 874)-were tested for association of the rs13266634 variant with measures of skeletal muscle response to resistance exercise. Our results were sexually dimorphic in both cohorts. Men in the EMD study with two copies of the protective allele showed less post-exercise bout strength loss, less soreness, and lower creatine kinase values. In addition, men in the FAMuSS, homozygous for the protective allele, showed higher pre-exercise strength and larger arm skeletal muscle volume, but did not show a significant difference in skeletal muscle hypertrophy or strength with resistance training.

Nicotine consumption is regulated by a human polymorphism in dopamine neurons

Smoking is the most important preventable cause of morbidity and mortality worldwide. Recent genome-wide association studies highlighted a human haplotype on chromosome 15 underlying the risk for tobacco dependence and lung cancer. Several polymorphisms in the CHRNA3-CHRNA5-CHRNB4 cluster coding for the nicotinic acetylcholine receptor (nAChR) α3, α5 and β4 subunits were implicated. In mouse models, we define a key role in the control of sensitivity to nicotine for the α5 subunit in dopaminergic (DAergic) neurons of the ventral tegmental area (VTA). We first investigated the reinforcing effects of nicotine in drug-naive α5(-/-) mice using an acute intravenous nicotine self-administration task and ex vivo and in vivo electrophysiological recordings of nicotine-elicited DA cell activation. We designed lentiviral re-expression vectors to achieve targeted re-expression of wild-type or mutant α5 in the VTA, in general, or in DA neurons exclusively. Our results establish a crucial role for α5*-nAChRs in DAergic neurons. These receptors are key regulators that determine the minimum nicotine dose necessary for DA cell activation and thus nicotine reinforcement. Finally, we demonstrate that a single-nucleotide polymorphism, the non-synonymous α5 variant rs16969968, frequent in many human populations, exhibits a partial loss of function of the protein in vivo. This leads to increased nicotine consumption in the self-administration paradigm. We thus define a critical link between a human predisposition marker, its expression in DA neurons and nicotine intake.

Association of Variant rs7903146 (C/T) Single Nucleotide Polymorphism of TCF7L2 Gene With Impairment in Wound Healing Among North Indian Type 2 Diabetes Population

The variants of transcription factor 7-like 2 (TCF7L2) gene have been shown to be associated with type 2 diabetes mellitus (T2DM) and its several secondary complications. Here, we aimed to examine the possible role of one of the common variant of this gene, rs7903146 (C/T), with impairment of wound healing in cases with T2DM. A total of 750 individuals, including 322 patients with T2DM and 120 patients with diabetic foot ulcers (DFUs) and 308 controls, were analyzed for rs7903146 variant of the TCF7L2 gene. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism. For rs7903146 variant, TT genotype frequency in patients with DFU was 10.8% and in controls was 5.2%. Risk genotype (TT) frequencies showed statistically significant difference between the DFU patients versus non-DM control group (odds ratio = 2.44, P = .037, 95% confidence interval = 1.05-5.64) compared with nonrisk genotype (CC + CT). In the present study, a positive significant association between DFU and the TT genotype of rs7903146 (C/T) variant of TCF7L2 gene was found.

Disease associated clinical factors and FTO polymorphism: effect on body mass in children with type 1 diabetes mellitus.

One of the consequences of excessive weight gain during insulin therapy in type 1 diabetes mellitus (T1DM) is an increased predisposition to cardiovascular diseases (CVD). Not only clinical but also genetic factors may play a role in the pathogenesis of this phenomenon. The aim of this study was to evaluate the prevalence of cardiovascular disease risk factors as well as the fat mass and obesity associated (FTO) gene rs9939609 variant in a large group of children with T1DM of the same ethnic-Polish origin. A total of 1237 children with T1DM and 1015 controls were recruited. The proportions of patients with obesity, hypertension, and abnormal LDL-cholesterol levels among children with T1DM were significantly higher than those in the non-diabetic. There was a higher rate of overweight, central obesity, and abnormal LDL-cholesterol levels among girls in comparison to that in boys in the group of children with diabetes. Children with inadequate metabolic control were characterized by the presence of more CVD risk factors. Similar differences were observed in children treated with the use of pens versus those using insulin pumps. The FTO gene single nucleotide polymorphism (SNP) correlated with body mass index (BMI) in both control and diabetic children, but the effect was lesser in diabetics. In a regression model the current BMI-SDS value in diabetics was significantly affected by the baseline BMI, disease duration, metabolic control, and subject's sex, but not the FTO genotype. Clinical rather than genetic factors have a greater impact on the development of overweight and obesity in insulin-treated children

Polymorphisms of transcription factor-7-like 2 (TCF7L2) gene in Tunisian women with polycystic ovary syndrome (PCOS)

Background and aimsPolycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women in their child-bearing age, and is often associated with insulin resistance and type 2 diabetes (T2DM). Given the overlap between PCOS and T2DM, we investigated the association of transcription factor-7-like 2 (TCF7L2) variants rs4506565, rs7903146, rs12243326, and rs12255372 with the susceptibility to PCOS. Subjects and methodsStudy subjects comprised 119 Tunisian women with PCOS (mean age 29.8±4.7years), and 150 control women (mean age 30.6±5.9years). TCF7L2 genotyping was done by the allelic discrimination/real-time PCR method. ResultsMinor allele frequencies (MAFs) of rs4506565 (P=0.61), rs7903146 (P=0.68), rs12243326 (P=0.56), and rs12255372 (P=0.60) were comparable between PCOS cases and control subjects. As the four tested TCF7L2 variants were in linkage disequilibrium, 4-locus (rs4506565, rs7903146, rs12243326, rs12255372) haplotype analysis demonstrated that haplotype 2111 was initially negatively associated with PCOS [P=0.035; OR (95% CI)=0.13 (0.02–0.85)], which was later lost upon correcting for multiple comparisons [Pc=0.248]. ConclusionOur data suggest that there is weak or no contribution of TCF7L2 gene polymorphism to PCOS in Tunisian women. Further studies with larger samples are necessary to confirm this observation.

Heterozygote of PLCE1 rs2274223 increases susceptibility to human papillomavirus infection in patients with esophageal carcinoma among the Kazakh populations

The involvement of human papillomavirus (HPV) in the carcinogenesis of esophageal squamous carcinoma remains undetermined. However, three genome-wide association studies of esophageal cancer have identified a shared susceptibility locus at 10q23 (rs2274223: A5780G) in phospholipase C epsilon 1 (PLCE1). The current study aims to present a comprehensive and novel spectrum about the HPV genotype distribution of esophageal carcinoma in Kazakhs and assess its association with PLCE1 polymorphisms. The HPV genotypes in 183 patients with esophageal cancer and 89 controls selected from the Kazakh population were evaluated using the HPV gene chip. The PLCE1 rs2274223 variant was genotyped in esophageal carcinoma patients by MALDI-ToF Mass Spectrometry. The presence of seven HPV genotypes in esophageal carcinoma tissues-including HPV 16, 18, 35, 52, 6, 11, 43-was significantly higher at 31.7% than those in controls at 9.0% (P < 0.001). Such presence was strongly associated with increased risk of esophageal carcinoma (OR 4.70; 95% CI 2.13-10.36). Among all HPV genotypes detected, HPV16 was the most common genotype identified (29.0%, OR 4.13; 95% CI 1.87-9.13), which is significantly associated with well-differentiated esophageal carcinoma (P = 0.037). HPV-positive patients were generally younger than HPV-negative patients (70.1% vs. 29.3%, P = 0.013). PLCE1 rs2274223 genotypes AG and AG/GG were significantly associated with HPV-positive patients with esophageal carcinoma (OR 2.05, 95% CI 1.03-4.08 and OR 1.98, 95% CI 1.02-3.84, respectively). These findings suggest that heterozygote of PLCE1 rs2274223 increases susceptibility to HPV infection in patients with esophageal carcinoma among the Kazakh populations.