Impact of CYP3A5 and MDR-1 gene polymorphisms on the dose and level of tacrolimus among living-donor liver transplanted patients: single center experience

Aim of work: To assess the impact of Cytochrome P450 3A5 (CYP3A5) and multidrug resistance-1 gene (MDR-1) single nucleotide polymorphisms on the dose and blood level of tacrolimus among liver transplanted patients.

Patients and methods: We enrolled a prospective study of 41 liver transplanted patients. Dose-adjusted trough blood concentration (C/D ratio) was calculated. Polymerase chain reaction-restriction fragment length polymorphism followed by sequencing was done for genotyping of CYP3A5*3 (6986A?>?G).

Results: At 1 week, 1 and 3 months C/D ratio were significantly lower in CYP3A5 expressers *1/*1 patients compared to non-expressers *3/*3.

Conclusion: CYP3A5 (6986A?>?G) genotype, rather than MDR-1 (2677G?>?A/T) variant, has an impact on tacrolimus pharmacokinetics.     

Forkhead box A1 (FOXA1) tagging polymorphisms and esophageal cancer risk in a Chinese population: a fine-mapping study

Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Esophageal squamous cell carcinoma (ESCC) accounts for more than 90% of esophageal cancers. Besides environmental risk factors, genetic factors such as single-nucleotide polymorphisms (SNPs) play an important role in ESCC carcinogenesis. We performed a hospital-based case–control study to evaluate the Forkhead-box protein A1 (FOXA1) rs12894364 C?>?T, rs2145146 C?>?A and rs7144658 T?>?C tag SNPs in the risk of developing ESCC. We recruited 629 ESCC cases and 686 controls. Genotypes were determined using ligation detection reaction. Logistic regression analyses revealed that the three FOXA1 SNPs were not associated with ESCC risk. However, there was significantly decreased ESCC risk associated with the FOXA1 rs12894364 C?>?T and rs2145146 C?>?A polymorphisms among older patients. There was significantly increased ESCC risk associated with the FOXA1 rs7144658 T?>?C polymorphism among male patients. This study demonstrates an association between FOXA1 polymorphisms and ESCC susceptibility. Additional larger studies are required to confirm our findings.     

Genetic polymorphisms of XRCC1 gene and susceptibility to gastric cancer in Chinese Han population

Abstract

This study aims to evaluate whether the c.1471G?>?A and c.1686C?>?G genetic polymorphisms of XRCC1 gene influencing gastric cancer susceptibility. A total of 813 subjects with Chinese Han ethnicity were enrolled. Our data suggest that the allele and genotype frequencies are significantly different from gastric cancer patients with cancer-free controls. We find that c.1471G?>?A and c.1686C?>?G genetic polymorphisms statistically increase the risk of gastric cancer. Our findings indicate these two genetic polymorphisms are related with the susceptibility to gastric cancer, and could be used as molecular markers for detecting gastric cancer in Chinese Han ethnicity.     

Research on association between variants and haplotypes of TRPV1 and TRPA1 genes with growth traits in three cattle breeds

The objective of this study was to examine the association of transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) genes polymorphisms with growth traits in three Chinese cattle breeds (Jiaxian red cattle, Qinchuan cattle and Luxi cattle). Through experiments we identified three single nucleotide polymorphisms (SNPs) in these three cattle breeds TRPV1 and TRPA1 genes using PCR-SSCP, (forced) PCR-RFLP methods. Three of these polymorphisms are all synonymous mutation which includes (NW_003104493.1: 30327 C?>?T), (NW_003104493.1: 33394 A?>?G) and (NW_003104493.1: 38471?G?>?A) are in exons. The other three polymorphisms are located at 3'UTR. Furthermore, we evaluated the haplotype frequency and the statistical analyses indicated that these SNPs of TRPV1 and TRPA1 genes were associated with bovine body height, body length, waist angle width, hucklebone width, cross ministry height, chest qingwidth (p?<?0.05) and recommendation height, cannon circumference (p?<?0.01) of Qingchuan cattle; body length, waist angle width (p?<?0.05) of Jiaxian red cattle; body weight, Body length, cannon circumference, chest circumference (p?<?0.05) and body height (p?<?0.01) of Luxi cattle. Our result confirms the polymorphisms in the TRPV1 and TRPA1 genes are associated with growth traits that may be used for marker-assisted selection (MAS) in three beef breeds programs.     

The contribution of SIPA1 and RRP1B germline polymorphisms to breast cancer phenotype,lymph node status and survival in a group of Lithuanian young breast cancer patients

The germline polymorphisms in signal-inducing proliferation-associated protein 1 (SIPA1) and ribosomal RNR processing 1B (RRP1B) might be involved in breast cancer metastasis. The aim of this study was to analyze how SIPA1 and RRP1B polymorphisms contribute to breast cancer phenotype, lymph node status and survival. A group of 100 young, I–II stage breast cancer patients were analyzed for SIPA1 and RRP1B polymorphisms with PCR-RFLP assay. SIPA1 c.2760G?>?A, c.545C?>?T and RRP1B c.436T?>?C polymorphisms were associated with lymph node status, survival and tumor grade, respectively. Our results suggest that SIPA1 and RRP1B germline polymorphisms are important for breast cancer prognosis.     

Polymorphism identification in GDF9 gene and its association analysis with reproduction traits in Jinghai Yellow chicken

Abstract

GDF9 (growth differentiation factor 9) belongs to the transforming growth factor-β (TGF-β) superfamily and plays an irreplaceable role in female fertility. To reveal its genetic effects on productivity performance in chickens, 373 Jinghai Yellow chickens were chosen randomly to detect SNPs in GDF9 by PCR-SSCP and DNA sequencing methods. Eventually, four SNPs (g.2053G?>?A, g.2275T?>?C, g.2338C?>?T, g.2420T?>?C) in total had been detected. Amongst them, g.2420T?>?C was first found significantly associated with reproduction trait in chickens and heterozygous type C₂T₂ had higher average egg weight at 300?days of age (AEWD300) than T₂T₂ (p?<?0.01). Least squares analysis showed that age at first laying (AFE) of H1 and H1H1 chickens were significantly earlier than that of H7 and H7H7 ones, respectively (p?<?0.05). H1H5 hens showed higher AEWD300 than H4H7 ones (p?<?0.05). For total egg number at 300?days of age (END300), mean of H5H5 was significantly higher than that of H4H4 (p?<?0.05). Hence, the study suggested that hybrid vigor at g.2420T?>?C could be utilized in practice. H1H1, H1H5 and H5H5 could be the dominant diplotypes for chicken breeding. The study may contribute to the breeding progress of productive chickens and supply reference for oviparous animal production practice.     

Association of <Emphasis Type="Italic">IL-10</Emphasis> gene (−1082A&gt;G, −819C&gt;T and −592C&gt;A) polymorphism and its serum level with metabolic syndrome of north Indian subjects

Metabolic syndrome (MetS) is an inflammatory disorder, in which various cytokines play important role in tilting balance towards disease state. Interleukin-10 (IL-10) is an important antiinflammatory cytokine, but its genetic polymorphisms and serum levels in Indian MetS subjects are unknown. Three IL-10 gene polymorphisms (?1082A >G (rs1800896), ?819C >T (rs1800872) and ?592C >A (rs1800871)) were genotyped with PCR-RFLP in MetS subjects (n = 384) and age/sex matched control subjects (n = 386). Serum IL-10 was measured using enzyme-linked immunosorbent assay. Serum IL-10 level was significantly low in MetS subject and significantly correlated with clinicobiochemical parameters of MetS. Of three investigated promoter polymorphisms, IL-10 –819C > T and –592C >A were significantly associated with risk of MetS. The mutant alleles ?819T and ?592A of IL-10 gene polymorphism were significantly higher in MetS subjects compared to controls. Of the four different haplotypes obtained, common ACC haplotype and rare GTA haplotype of IL-10 polymorphisms were associated with MetS. The mean of fasting insulin and HOMA-IR were significantly different between the genotypes of both ?819 C >T and ?592C >A polymorphisms of IL-10 in MetS subjects. These results suggested that polymorphisms in IL-10 gene (?819C >T and ?592C >A), haplotypes (ACC and GTA) and serum level are significantly associated with risk of MetS. IL-10 ?819C >T and ?592C >A polymorphic variants are also significantly associated with insulin level and homeostasis model assessment-insulin resistance in north Indian MetS subjects.     

Association of the variants and haplotypes in the DOCK7, PCSK9 and GALNT2 genes and the risk of hyperlipidaemia

Little is known about the association between the single nucleotide polymorphisms (SNPs) and haplotypes of the dedicator of cytokinesis 7 (DOCK7), pro‐protein convertase subtilisin/kexin type 9 (PCSK9) and polypeptide N‐acetylgalactosaminyltransferase 2 (GALNT2) and serum lipid traits in the Chinese populations. This study was to determine the association between nine SNPs in the three genes and their haplotypes and hypercholesterolaemia (HCH)/hypertriglyceridaemia (HTG), and to identify the possible gene–gene interactions among these SNPs. Genotyping was performed in 733 HCH and 540 HTG participants. The haplotype of C‐C‐G‐C‐T‐G‐C‐C‐G [in the order of DOCK7 rs1168013 (G>C), rs10889332 (C>T); PCSK9 rs615563 (G>A), rs7552841 (C>T), rs11206517 (T>G); and GALNT2 rs1997947 (G>A), rs2760537 (C>T), rs4846913 (C>A) and rs11122316 (G>A) SNPs] was associated with increased risk of HCH and HTG. The haplotypes of C‐C‐G‐C‐T‐G‐C‐C‐A and G‐C‐G‐T‐T‐G‐T‐C‐G were associated with a reduced risk of HCH and HTG. The haplotypes of G‐C‐G‐C‐T‐G‐C‐C‐A and G‐C‐G‐C‐T‐G‐T‐C‐G were associated with increased risk of HCH. The haplotypes of C‐T‐G‐C‐T‐G‐C‐C‐G, G‐C‐A‐C‐T‐G‐C‐C‐G and G‐C‐G‐C‐T‐G‐C‐C‐A were associated with an increased risk of HTG. The haplotypes of G‐C‐G‐C‐T‐G‐T‐C‐A and G‐C‐G‐T‐T‐G‐T‐C‐G were associated with a reduced risk of HTG. In addition, possible inter‐locus interactions among the DOCK7, PCSK9 and GALNT2 SNPs were also noted. However, further functional studies of these genes are still required to clarify which SNPs are functional and how these genes actually affect the serum lipid levels.     

Association of NADPH oxidase p22phox gene C242T, A640G and −930A/G polymorphisms with primary knee osteoarthritis in the Greek population

Osteoarthritis (OA) is the most common form of arthritis with still unknown pathogenic etiology and considerable contribution of genetic factors. Recently, a new emerging role of oxidative stress in the pathology of OA has been reported, lacking however elucidation of the underlying mechanism. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase being a complex enzyme produced by chondrocytes, presents the major source of reactive oxygen species and main contributor of increased oxidative stress. The present study aims to evaluate the association of NADPH oxidase p22phox gene C242T, A640G and ?A930G polymorphisms with primary knee OA in the Greek population. One hundred fifty five patients with primary symptomatic knee OA participated in the study along with 139 matched controls. Genotypes were determined using polymerase chain reaction and restriction fragment length polymorphism technique. Allelic and genotypic frequencies were compared between both study groups. NADPH p22phox ?A930G polymorphism was significantly associated with knee OA in the crude analysis (P = 0.018). No significant difference was detected for C242T and A640G polymorphisms (P > 0.05). The association between ?A930G polymorphism and knee OA disappeared when the results were adjusted for obesity (P = 0.078, odds ratio 0.54, 95 % CI 0.272–1.071). The interaction between all three polymorphisms was not significant. The present study shows that NADPH oxidase p22phox gene C242T, A640G and ?A930G polymorphisms are not risk factors for knee OA susceptibility in the Greek population. Further studies are needed to give a global view of the importance of this polymorphism in the pathogenesis of OA.     

Association of +45(T/G) and +276(G/T) polymorphisms in the adiponectin gene with coronary artery disease in a population of Iranian patients with type 2 diabetes

The relation of Two single nucleotide polymorphisms (SNPs) at the adiponectin locus (+45T/G and +276G/T) with coronary artery disease (CAD) is controversial. The aim of the present study was to evaluate the genetic influence of the adiponectin gene polymorphisms in the development of CAD among patients with Type 2 diabetes (T2D). The adiponectin genotypes were detected by polymerase chain reaction and restriction analysis (PCR-RFLP) in our patients. Two adiponectin gene (ADIPOQ) SNPs (i.e. SNPs +45T>G and +276G>T) were genotyped in 114 Type 2 diabetic subjects with CAD, and 127 Type 2 diabetic patients without CAD. Demographic and anthropometric data along with plasma biochemistry including lipids, glycemic indices, and adiponectin were collected. There was a significant difference in the distribution of genotypes of +45T/G and +276G/T between CAD and non-CAD individuals (P < 0.05). Based on our results SNP+276G>T is associated with decreased risk of CAD after adjustment for potential confounding factors [adjusted OR = 0.39 (95%CI: 0.22–0.68); P = 0.001]. Similar findings were not observed for the +45T>G SNP. Two haplotypes 45T-276T and 45G-276T were associated with a decreased risk of CAD [adjusted OR = 0.47 (95% CI: 0.32–0.94); P = 0.03 and adjusted OR = 0.33 (95% CI: 0.13–0.83); P = 0.02 respectively]. No significant difference was observed between HOMA-IR, BMI, waist circumference, history of hypertension, HbA1C, and lipid concentrations regarding the two SNPs. In conclusion, these findings suggest that T allele of +276G>T SNP is significantly associated with decreased risk of CAD in T2D Patients. Also Haplotype analysis showed that two haplotypes 45T-276T and 45G-276T were associated with a decreased risk of CAD.     

Association between single nucleotide polymorphisms of TPH1 and TPH2 genes,and depressive disorders

Tryptophan catabolites pathway disorders are observed in patients with depression. Moreover, single nucleotide polymorphisms of tryptophan hydroxylase genes may modulate the risk of depression occurrence. The objective of our study was to confirm the association between the presence of polymorphic variants of TPH1 and TPH2 genes, and the development of depressive disorders. Six polymorphisms were selected: c.804‐7C>A (rs10488682), c.‐1668T>A (rs623580), c.803+221C>A (rs1800532), c.‐173A>T (rs1799913)—TPH1, c.‐1449C>A (rs7963803), and c.‐844G>T (rs4570625)—TPH2. A total of 510 DNA samples (230 controls and 280 patients) were genotyped using TaqMan probes. Among the studied polymoorphisms, the G/G genotype and G allele of c.804‐7C>A—TPH1, the T/T homozygote of c.803+221C>A—TPH1, the A/A genotype and A allele of c.1668T>A—TPH1, the G/G homozygote and G allele of c.‐844G>T—TPH2, and the C/A heterozygote and A allele of c.‐1449C>A—TPH2 were associated with the occurrence of depression. However, the T/T homozygote of c.‐1668T>A—TPH1, the G/T heterozygote and T allele of c.‐844G>T—TPH2, and the C/C homozygote and C allele of c.‐1449C>A—TPH2 decreased the risk of development of depressive disorders . Each of the studied polymorphisms modulated the risk of depression for selected genotypes and alleles. These results support the hypothesis regarding the involvement of the pathway in the pathogenesis of depression.     

Association of <Emphasis Type="Italic">Cytotoxic T Lymphocyte-associated antigen-4</Emphasis> gene haplotype with the susceptibility to gastric cancer

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) was widely accepted as a pivotal molecule in downregulating T-cell mediated immune responses. In this study we investigated the polymorphisms which would impact the CTLA-4 gene expression and function to assess the association with the risk of gastric cancer. 205 gastric cancer patients and 262 healthy controls were included in the case-control study. PCR and restriction fragment length polymorphism (RFLP) methods were performed to identify the +49A/G and promoter −1661A/G polymorphisms. The promoter −1772T/C polymorphism was detected by PCR amplification refractory mutation system (ARMS) technique. A significant difference was observed between case and control groups. The frequency of +49A/G polymorphism AG and −1661A/G polymorphism GG genotype were significantly higher in patients than in controls (OR = 2.15, OR = 1.88, respectively). No significant difference was found in the allelic frequency of −1772T/C polymorphism between cases and controls (P = 0.478). By the haplotype analysis, logistic regression showed the frequency of haplotype A (GAT) and D (AGT) in the case group revealed significant difference compared with in control group(OR = 2.00, P < 0.001; OR = 1.62, P = 0.043, respectively). Our findings implied the genetic variations within CTLA-4 gene would be a critical risk factor to the susceptibility of gastric cancer.     

Associations of polymorphisms in TXNIP and gene–environment interactions with the risk of coronary artery disease in a Chinese Han population

Single nucleotide polymorphisms (SNPs) in thioredoxin‐interacting protein (TXNIP) gene may modulate TXNIP expression, then increase the risk of coronary artery disease (CAD). In a two‐stage case–control study with a total of 1818 CAD patients and 1963 controls, we genotyped three SNPs in TXNIP and found that the variant genotypes of SNPs rs7212 [odds ratio (OR) = 1.26, P = 0.001] and rs7211 (OR = 1.23, P = 0.005) were significantly associated with increased CAD risk under a dominant model. In haplotype analyses, compared with the reference haplotype, haplotype ‘G‐T’ had a 1.22‐fold increased risk of CAD (P = 0.003). We also observed the cumulative effects of SNPs rs7212 and rs7211 on CAD risk and the severity of coronary atherosclerosis. Moreover, the gene–environment interactions among the variant genotypes of SNP rs7212, smoking habit, alcohol drinking habit and history of type 2 diabetes were associated with a 3.70‐fold increased risk of CAD (P < 0.001). Subsequent genotype‐phenotype correlation analyses further observed the significant effects of SNP rs7212 on TXNIP mRNA expression, plasma TXNIP and malondialdehyde levels. Taken together, our data suggest that TXNIP SNPs may individually and cumulatively affect CAD risk through a possible mechanism for regulating TXNIP expression and gene–environment interactions.     

Low-density lipoprotein-associated variables and the severity of coronary artery disease: an untreated Chinese cohort study

Abstract

Background and aims: Elevated low-density lipoprotein cholesterol (LDL-C) is causal risk for coronary artery disease (CAD) and LDL-associated variables including LDL-C, apolipoprotein B (apoB), non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein a [Lp(a)], small dense LDL (sd-LDL), and oxidized LDL (ox-LDL) have been widely used for predicting the risk of CAD. This study was aimed to compare the values of six LDL-related variables for predicting the severity of CAD using untreated patients undergoing coronary angiography (CAG).

Methods: A group of 1977 individuals were consecutively enrolled and divided into CAD (n?=?1151) and non-CAD groups (n?=?826) according to the results of CAG. LDL-C, apoB, non-HDL-C, Lp(a), sd-LDL and ox-LDL were measured, respectively. The numbers of stenotic arteries and Gensini Scores (GS) were used to calculate the severity of CAD and the associations of six variables with the severity of CAD and predicting value of these parameters were simultaneously examined.

Results: CAD patients had significantly higher concentrations of LDL-related variables than non-CAD ones (all p?<?0.05). Importantly, all variables rose with the increase in the severity of CAD. The predicting value of CAD manifested as sd-LDL?>?ox-LDL?>?apoB?>?non-HDL-C?>?LDL-C?>?Lp(a) [area under curve (AUC): sd-LDL 0.641; ox-LDL 0.640; apoB 0.611; non-HDL-C 0.587; LDL-C 0.583; Lp(a) 0.554; respectively]. In multivariate logistic analysis, all variables showed as independent risk factors for the severity of CAD [odds ratio (OR): ox-LDL?>?sd-LDL?>?apoB?>?non-HDL-C?>?LDL-C?>?Lp(a)].

Conclusions: All of LDL-related variables could be useful marker for predicting the severity of CAD but sd-LDL and ox-LDL appeared to litter better. Further study may be needed to validate our results.     

G allele of the −930A>G polymorphism of the CYBA gene is associated with insulin resistance in obese subjects

It has been shown that NADPH oxidase plays a role in oxidative stress which has been involved in the development of metabolic syndrome. The ?930A/G polymorphism of the CYBA gene (that codes p22phox, a major component of the NADPH oxidase) has been associated with human hypertension and with a reduction in NADPH oxidase activity. In this work, we have examined the influence of the ?930A/G polymorphism on obesity risk and insulin resistance in a case-control study of Spanish subjects (n=313). In the obese group (n=159), there was a statistically significant association between the GG genotype of the ?930A/G polymorphism of the CYBA gene and fasting insulin levels and HOMA index. This outcome agrees with previous findings concerning functional analyses of this polymorphism and reinforces the hypothesis that insulin resistance is associated with oxidative stress. In conclusion, a protective effect in carriers of the ?930A/G, polymorphism of the p22phox gene against insulin resistance in a population of Spanish obese adults has been found.     

Adiponectin gene variants and the risk of coronary artery disease in patients with type 2 diabetes

Patients with type 2 diabetes (T2D) are more susceptible to develop cardiovascular complications than non-diabetic subjects. Several studies have indicated a role of adiponectin gene in the increased coronary artery disease (CAD) risk in T2D patients. The data however is limited and have been inconsistent. In this study we examined the association of SNP45T>G and SNP276G>T of adiponectin gene with CAD risk in T2D patients in a Saudi population. A total of 418 type 2 diabetic patients were randomly recruited in this study from the RIYADH COHORT. Of the total diabetes patients, 123 were also diagnosed to have CAD, while the rest were control subjects. Anthropometric, clinical and biochemical parameters were measured by standard procedures. Genotyping of polymorphisms was carried out by PCR–RFLP analysis. Genotype distribution of SNP45T>G was significantly (P = 0.005) different between control and CAD subjects, while the distribution of SNP276G>T genotypes was comparable between the subjects. The SNP45T>G was significantly associated with risk of CAD [OR (95% CI), 4.7 (1.6–13.5), P < 0.003] but not SNP276G>T [OR (95% CI), 1.02 (0.53–1.9), P > 0.05]. The association of SNP45T>G with CAD risk remained significant even after adjusting for potential confounding factors [OR (95% CI), 7.2 (1.1–45.9), P < 0.05]. The SNP45T>G of adiponectin gene is an independent risk factor for CAD in T2D patients in a Saudi population. These findings support a role for adiponectin gene in the increased CAD risk in diabetes patients and are consistent with genetic heterogeneity in the association between adiponectin gene and coronary artery disease.     

Prion protein gene sequence and chronic wasting disease susceptibility in white-tailed deer (Odocoileus virginianus)

ABSTRACT

The sequence of the prion protein gene (PRNP) affects susceptibility to spongiform encephalopathies, or prion diseases in many species. In white-tailed deer, both coding and non-coding single nucleotide polymorphisms have been identified in this gene that correlate to chronic wasting disease (CWD) susceptibility. Previous studies examined individual nucleotide or amino acid mutations; here we examine all nucleotide polymorphisms and their combined effects on CWD. A 626 bp region of PRNP was examined from 703 free-ranging white-tailed deer. Deer were sampled between 2002 and 2010 by hunter harvest or government culling in Illinois and Wisconsin. Fourteen variable nucleotide positions were identified (4 new and 10 previously reported). We identified 68 diplotypes comprised of 24 predicted haplotypes, with the most common diplotype occurring in 123 individuals. Diplotypes that were found exclusively among positive or negative animals were rare, each occurring in less than 1% of the deer studied. Only one haplotype (C, odds ratio 0.240) and 2 diplotypes (AC and BC, odds ratios of 0.161 and 0.108 respectively) has significant associations with CWD resistance. Each contains mutations (one synonymous nucleotide 555C/T and one nonsynonymous nucleotide 286G/A) at positions reported to be significantly associated with reduced CWD susceptibility. Results suggest that deer populations with higher frequencies of haplotype C or diplotypes AC and BC might have a reduced risk for CWD infection – while populations with lower frequencies may have higher risk for infection. Understanding the genetic basis of CWD has improved our ability to assess herd susceptibility and direct management efforts within CWD infected areas.     

Gender‐Specific Association of a Perilipin Gene Haplotype with Obesity Risk in a White Population

Objective: Perilipin is a class of protein‐coating lipid droplets in adipocytes and steroidogenic cells. Our purpose was to examine the association between common single‐nucleotide polymorphisms (SNPs) at the perilipin (PLIN) locus and obesity, as well as related phenotypes, in unrelated American adults. Research Methods and Procedures: Four PLIN SNPs (PLIN 6209T>C, 11482G>A, 13041A>G, and 14995A>T) were typed in 734 white subjects (373 men and 361 women) attending a residential lifestyle intervention program. The baseline anthropometric and biochemical measures were used. Obesity was defined as BMI ≥ 30 kg/m². Results: Multivariate analysis demonstrated that, in women, two of the SNPs (13041A>G, and 14995A>T) were significantly associated with percentage body fat (p = 0.016 for 13041A>G and p = 0.010 for 14995A>T) and waist circumference (p = 0.020 for 13041A>G and p = 0.045 for 14995A>T). Moreover, haplotype analysis using these two SNPs indicated that haplotypes A/T and G/T were both associated with significantly increased obesity risk (odds ratio = 1.76, 95% confidence interval 1.07 to 2.90 for haplotype A/T, and odds ratio = 1.73, 95% confidence interval 1.06 to 2.82 for haplotype G/T) when compared with haplotype A/A. No significant associations between PLIN variations and obesity were found in men. Discussion: Our data support the hypothesis that the PLIN locus may be a significant genetic determinant for obesity risk in whites and that women are more sensitive to the genetic effects of perilipin than men.